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Results for “Molecular Docking Simulation”

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PubMed1998

Conformational analysis and automated receptor docking of selective arylacetamide-based kappa-opioid agonists.

The three-dimensional structure, dynamics, and binding modes of representative kappa-opioid agonists of the arylacetamide class (U50, 488; U69,593; U62,066; CI-977; ICI199,441; ICI197,067; BRL52,537; and BRL52,656) have been investigated using molecular modeling techniques. Systematic exploration of the conformational space of the ligand combined with molecular dynamics (MD) simulations in water revealed consistent conformational preferences for all the kappa-agonists in this series. The results were further compared with available X-ray and 1D- and 2D-NMR data to identify potential "lead" conformers for molecular docking. Ligand binding modes were initially determined using automated docking of two of the ligands (U50,488 and BRL52,537) to the kappa-opioid receptor. Extrapolation of the predicted binding mode to other members in this ligand series revealed similar docking preferences, with each ligand docked along the receptor helical axis. The binding modes were further refined using MD simulations of the receptor-ligand complexes. The results show a that salt bridge is formed between the amino proton of the ligands and the carboxylate group of Asp138 in TM3. This interaction most likely serves as a key anchoring point for the agonist association. Additional ligand contacts were noted with kappa-specific residues Ile294, Leu295, and Ala298, which may, in part, explain the kappa-selectivity in this series. In comparing the arylacetamides with opiate-based ligands, no evidence was found to link these classes through a common binding motif (except for the ion pair). The binding site model was also applied to explain the enantiomeric preference of U50,488 and to provide insight to the mu/kappa-selectivity of representative ligands in this series. Overall, the results provide a structure-based rationale for ligand recognition that is consistent both with site-directed mutagenesis experiments and structure-function relationship data.

Acetamides↗

PubMed2006

Exploring the molecular basis of the enantioselective binding of penicillin G acylase towards a series of 2-aryloxyalkanoic acids: a docking and molecular dynamics study.

In the present paper, molecular modeling studies were undertaken in order to shed light on the molecular basis of the observed enantioselectivity of penicillin G acylase (PGA), a well known enzyme for its industrial applications, towards 16 racemic 2-aryloxyalkanoic acids, which have been reported to affect several biological systems. With this intention docking calculations and MD simulations were performed. Docking results indicated that the (S)-enantiomers establish several electrostatic interactions with SerB1, SerB386 and ArgB263 of PGA. Conversely, the absence of specific polar interactions between the (R)-enantiomers and ArgB263 seems to be the main reason for the different binding affinities observed between the two enantiomers. Results of molecular dynamics simulations demonstrated that polar interactions are responsible for both the ligand affinity and PGA enantiospecificity. Modeling calculations provided possible explanations for the observed enantioselectivity of the enzyme that rationalize available experimental data and could be the basis for future protein engineering efforts.

Alkanes↗

PubMed2000

Simulation of regulated exocytosis of amylase from salivary parotid acinar cells by a consecutive reaction model comprising two sequential first-order reactions.

Amylase secretion from parotid acinar cells results from stimulus-regulated fusion of apical membrane and secretory granules that contain amylase. The time course of amylase secretion induced by various secretagogues has been reported. Calcium-mobilizing agonists such as carbamylcholine and substance P induce rapid and transient secretion while cAMP-mobilizing agonists such as isoproterenol cause long-term secretion. Combination of these two types of agonists results in a rapid and high rate of secretion. To explain the various time courses of these stimulations, it was assumed that amylase secretion is a consecutive reaction that consists of two first-order reactions. It was postulated that secretory granules were classified into three states: (A) pre-docked, (B) docked, and (C) fusion. The simple simulation could explain the time course of amylase secretion induced by various secretagogues by simply changing the rate constants for docking (reaction A to B) and fusion (reaction B to C) steps. It was also found that calcium mainly enhances the last fusion step and that cAMP activates the docking step. The amount of docked granules is estimated to be quite small, which accounts for why amylase secretion is regulated mainly by cAMP. The effects of the two types of secretagogues were synergistic, meaning that their intracellular signaling pathways are independent. At the same time, this also suggests that basal and enhanced secretion induced by two types of agonists have the same exocytotic process and that two stimuli independently activate the same machinery that mediates docking or fusion. This simulation is useful in analysis of the effects of secretion modulators and the molecular mechanism of amylase secretion.

Amylases↗

PubMed1995

Interaction of substrate uridyl 3',5'-adenosine with ribonuclease A: a molecular dynamics study.

A wealth of information available from x-ray crystallographic structures of enzyme-ligand complexes makes it possible to study interactions at the molecular level. However, further investigation is needed when i) the binding of the natural substrate must be characterized, because ligands in the stable enzyme-ligand complexes are generally inhibitors or the analogs of substrate and transition state, and when ii) ligand binding is in part poorly characterized. We have investigated these aspects in the binding of substrate uridyl 3',5'-adenosine (UpA) to ribonuclease A (RNase A). Based on the systematically docked RNase A-UpA complex resulting from our previous study, we have undertaken a molecular dynamics simulation of the complex with solvent molecules. The molecular dynamics trajectories of this complex are analyzed to provide structural explanations for varied experimental observations on the ligand binding at the B2 subsite of ribonuclease A. The present study suggests that B2 subsite stabilization can be effected by different active site groups, depending on the substrate conformation. Thus when adenosine ribose pucker is O4'-endo, Gln69 and Glu111 form hydrogen-bonding contacts with adenine base, and when it is C2'-endo, Asn71 is the only amino acid residue in direct contact with this base. The latter observation is in support of previous mutagenesis and kinetics studies. Possible roles for the solvent molecules in the binding subsites are described. Furthermore, the substrate conformation is also examined along the simulation pathway to see if any conformer has the properties of a transition state. This study has also helped us to recognize that small but concerted changes in the conformation of the substrate can result in substrate geometry favorable for 2',3' cyclization. The identified geometry is suitable for intraligand proton transfer between 2'-hydroxyl and phosphate oxygen atom. The possibility of intraligand proton transfer as suggested previously and the mode of transfer before the formation of cyclic intermediate during transphosphorylation are discussed.

Animals↗

PubMed1998

The roles of individual gamma-carboxyglutamate residues in the solution structure and cation-dependent properties of conantokin-T.

The solution structure of the Ca2+-loaded conantokin-T (con-T), a gamma-carboxyglutamate (Gla)-containing 21-residue peptide (NH2-G1EgammagammaY5QKMLgamma10NLRgammaA15EVKKN20A-CONH2,gam ma = Gla), has been elucidated by use of distance geometry calculations with experimental distances derived from two-dimensional 1H NMR spectroscopy. An end-to-end alpha-helix was the dominant conformation in solution, similar to that of apo-con-T, except that reorientation of several side chains occurred in the Ca2+-coordinated complex. The most notable examples of this were those of Gla10 and Gla14, which were more optimally positioned for complexation with Ca2+. In addition to the stabilization offered to the alpha-helix by Ca2+ binding, hydrophobic clustering of the side chains of Tyr5, Met8, Leu9, and Leu12, and ionic interactions between Lys7 and Gla3/Gla10 and between Arg13 and Gla14, along with hydrogen bonding between Gln6 and Gla10, were among the side chain interactions likely playing a significant role in maintenance of the alpha-helical conformation. Docking of Ca2+ in the con-T structure was accomplished using genetic algorithm-molecular dynamics simulation approaches. The results showed that one Ca2+ ion is most likely coordinated by four side chain oxygen atoms, two each from Gla10 and Gla14. Another bound Ca2+ ion has as its donor sites three oxygen atoms, two from Gla3 and one from Gln6. To examine the functional roles of the individual Gla residues, a series of variant peptides have been synthesized with Ala substituted for each Gla residue, and several properties of the resulting variants have been examined. The data obtained demonstrated the importance of Gla10 and Gla14 in stabilizing binding of the highest affinity Ca2+ site and in governing the conformational change induced by Ca2+. The critical nature of Gla3 and Gla4 in inhibition of the spermine-induced potentiation of the binding of MK-801 to open ion channels of the N-methyl-D-aspartate receptor was established, as well as the role of Gla4 in stabilizing the apo-con-T alpha-helical conformation.

1-Carboxyglutamic Acid↗

PubMed2026

Thyroid-stimulating hormone receptor mediates peripheral-central neuroimmune crosstalk in autoimmune thyroid diseases.

BACKGROUND: Organ-specific autoimmune diseases, particularly Graves' disease (GD) and its extrathyroidal manifestation, Graves' orbitopathy (GO), are characterized by systemic autoimmunity that may extend its impact to the central nervous system (CNS). While thyroid-stimulating hormone receptor (TSHR) is the primary driver of pathological remodeling in the thyroid and orbital tissues, emerging evidence suggests it is also expressed in the brain and may participate in neuroimmune signaling. However, the molecular mechanisms linking peripheral TSHR-driven autoimmunity to these extended systemic features remain unclear. Thus, GD and GO provide a unique window to investigate how peripheral autoantibodies influence CNS involvement as part of its broader pathological spectrum. METHODS: Genome-wide association studies (GWAS) and post-GWAS analyses were integrated with bulk RNA sequencing, single-cell and spatial transcriptomics, and brain imaging phenotypes to comprehensively characterize peripheral and central alterations in GD and GO. Mendelian randomization was applied to test causal relationships between genetic variants and brain signatures. Structural biology analyses were further conducted including protein-protein docking, small-molecule docking, and normal mode dynamics to identify prospective modulators of TSHR. Immunofluorescence staining was performed in a GO mouse model to validate the colocalization of potential interacted proteins in the specific brain region. RESULTS: Brain imaging-derived phenotypes (IDPs) alterations in GO and GO were systematically analyzed to identify neuroanatomical and functional alterations. TSHR was further identified as a shared genetic driver across peripheral and central compartments. TSHR was expressed in spiny projection neurons, microglia, and peripheral T cells, with cell-cell communication analyses highlighting TSHR-mediated interactions among neurons, endothelial cells, and microglia. Immunofluorescence staining in a GO mouse model confirmed the colocalization of TSHR with FN1 and GNAS in the basal ganglia, providing tissue-level validation of the computationally predicted ligand-receptor interactions. Immune profiling further showed immune alterations in GD and GO. Structural modeling supported plausible physical interfaces between TSHR and interacting proteins, and small-molecule screening identified three repurposable compounds - venetoclax, irinotecan, and dutasteride - with predicted favorable docking scores and stable binding poses in our simulations. CONCLUSIONS: These findings demonstrate that TSHR acts as a molecular hub mediating peripheral-central neuroimmune crosstalk in GD and GO. The results support a broader "disease-molecule axis" framework that links genetic susceptibility with multi-level immune and neural mechanisms. This work provides mechanistic insights relevant to the development of TSHR-targeted therapies, with implications for both peripheral immune modulation and central regulation. However, the limited sample size, lack of longitudinal follow-up, and absence of in vivo validation warrant cautious interpretation and further investigation.

Receptors, Thyrotropin↗

PubMed1995

Detection and geometric modeling of molecular surfaces and cavities using digital mathematical morphological operations.

We developed a digital method based on mathematical morphological operations to obtain three types of surfaces: van der Waals surface, solvent-accessible surface, and molecular surface, to extract the cavities on the surface and interior part of the molecule and to extract the ligand portions in contact with the cavities. The molecular surface, the cavities and the portions, and the heme region are visualized using solid modeling. The method enables us to obtain the volumes of the cavities and inhibitor portions and the areas of the surfaces. Solid modeling enables us to obtain cross-sections at arbitrary positions. This will have considerable utility in docking studies.

Computer Graphics↗

PubMed2005

Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor.

S-(+)-Norfenfluramine (SNF)-an active metabolite of the now-banned anorexigen fenfluramine-has been implicated in the drug's appetite-suppressing actions and its life-threatening cardiovascular side effects. SNF reduces appetite through serotonin 5-HT(2C) receptor activation; it causes cardiopulmonary side effects through 5-HT(2B) receptor activation. Thus, we attempted to identify molecular determinants of SNF binding to 5-HT(2B) receptors distinct from those underlying SNF-5-HT(2C/2A) receptor interactions. Mutagenesis implicated Val2.53 in SNF binding to 5-HT(2B) receptors. Ligand docking simulations suggested both Val2.53 gamma-methyl groups form stabilizing van der Waals' (vdW) interactions with the alpha-methyl group of SNF. A V2.53L mutation induced a 17-fold decrease in affinity; molecular dynamics (MD) simulations suggested that this decrease resulted from the loss of one 2.53-alpha-methyl group vdW interaction. Supporting this, 1) the binding of norfenfluramine (NF) analogs lacking an S-(+) alpha-methyl group (RNF and alpha-desmethyl-NF) was less sensitive to the V2.53L mutation, and 2) a V2.53A mutation decreased SNF affinity 190-fold, but decreased RNF and alpha-desmethyl-NF affinities only 16- and 45-fold, respectively. We next addressed whether the alpha-methyl group of SNF contributes to 5-HT(2C/2A) receptor affinity. Removal of the alpha-methyl group (RNF and alpha-desmethyl-NF), which reduced 5-HT(2B) receptor binding 3-fold, did not affect 5-HT(2C/2A) receptor binding. An alpha-ethyl substituent (alpha-ethyl-NF), which decreased 5-HT(2B) receptor affinity 46-fold, reduced 5-HT(2C) and 5-HT(2A) receptor binding by 14- and 5-fold, respectively. Finally, we determined that residue 2.53 affects SNF potency and efficacy at 5-HT(2B) receptors but not at 5-HT(2C) and 5-HT(2A) receptors. In conclusion, vdW interactions between residue 2.53 and the alpha-methyl group of SNF contribute to the ligand's 5-HT(2) receptor subtype-selective pharmacology.

Appetite Depressants↗

PubMed2005

Molecular modeling and molecular dynamics simulation of the human A2B adenosine receptor. The study of the possible binding modes of the A2B receptor antagonists.

A molecular model of the human A(2B) adenosine receptor containing seven transmembrane alpha helices connected by three intracellular and three extracellular hydrophilic loops had been constructed. A molecular docking of seven structurally diverse xanthine antagonists of the A(2B) receptor was performed, and the differences in their binding modes were investigated. The 1 ns molecular dynamics (MD) simulations of several obtained ligand-receptor complexes inserted into the phospholipid bilayer were carried out. The conformational changes of the A(2B) receptor occurring during MD simulations were explored, and the stable binding modes of the studied antagonists were determined. According to the models presented in this work, the involvement of the His251, Asn282, Ser92, Thr89, and some aromatic residues in ligand recognition was determined. The obtained binding modes of the A(2B) antagonists demonstrate good agreement with the site-directed mutagenesis data.

Adenosine A2 Receptor Antagonists↗

PubMed1996

Unraveling principles of lead discovery: from unfrustrated energy landscapes to novel molecular anchors.

The search for novel leads is a critical step in the drug discovery process. Computational approaches to identify new lead molecules have focused on discovering complete ligands by evaluating the binding affinity of a large number of candidates, a task of considerable complexity. A new computational method is introduced in this work based on the premise that the primary molecular recognition event in the protein binding site may be accomplished by small core fragments that serve as molecular anchors, providing a structurally stable platform that can be subsequently tailored into complete ligands. To fulfill its role, we show that an effective molecular anchor must meet both the thermodynamic requirement of relative energetic stability of a single binding mode and its consistent kinetic accessibility, which may be measured by the structural consensus of multiple docking simulations. From a large number of candidates, this technique is able to identify known core fragments responsible for primary recognition by the FK506 binding protein (FKBP-12), along with a diverse repertoire of novel molecular cores. By contrast, absolute energetic criteria for selecting molecular anchors are found to be promiscuous. A relationship between a minimum frustration principle of binding energy landscapes and receptor-specific molecular anchors in their role as "recognition nuclei" is established, thereby unraveling a mechanism of lead discovery and providing a practical route to receptor-biased computational combinatorial chemistry.

Binding Sites↗

PubMed2005

Dynamics of the native and the ligand-bound structures of eosinophil cationic protein: network of hydrogen bonds at the catalytic site.

Eosinophil Cationic Protein (ECP) is sequentially and structurally similar to ribonuclease A (RNase A). It belongs to the RNase A family of proteins and the RNA catalysis is essential to its biological function. In the present study, we have generated the dinucleotide-bound structures of ECP by docking the dinucleotides to a number of molecular dynamics (MD) generated ECP structures. The stability of the docked enzyme-ligand complexes was ascertained by extensive MD simulations. The modes of ligand binding are explored by essential dynamics studies. The role of water molecules in the stability of the complex and in the catalysis was investigated. The active site residues form a complex network of connections with the ligand and with a water molecule. The catalytic mechanism of the RNA cleavage is examined on the basis of the active site geometry obtained by the simulations.

Binding Sites↗

PubMed2004

Development of a 3D model for the human cannabinoid CB1 receptor.

A novel comparison model of the human cannabinoid CB1 receptor has been constructed using the bovine rhodopsin X-ray structure as a template. The model was subjected to a 500-ps molecular dynamics simulation, and thereafter new conformers of the receptor model were produced in a simulated annealing procedure. Using an automated docking procedure, well-known cannabimimetic ligands were docked into six different model conformers, of which one was chosen for a detailed study of receptor-ligand interactions. The docking results confirm, for example, the importance of lysine K3.28(192) in the binding of these ligands. Also, other experimental data are fairly consistent with the present model, though there are some differences when compared to other recent CB1 comparison models. The present model will serve as a tool to investigate the receptor-ligand interactions and facilitate the design of novel cannabimimetic drugs.

Amino Acid Sequence↗

PubMed2006

Model of the whole rat AT1 receptor and the ligand-binding site.

We present a three-dimensional model of the rat type 1 receptor (AT1) for the hormone angiotensin II (Ang II). Ang II and the AT1 receptor play a critical role in the cell-signaling process responsible for the actions of renin-angiotensin system in the regulation of blood pressure, water-electrolyte homeostasis and cell growth. Development of improved therapeutics would be significantly enhanced with the availability of a 3D-structure model for the AT1 receptor and of the binding site for agonists and antagonists. This model was constructed using a combination of computation and homology-modeling techniques starting with the experimentally determined three-dimensional structure of bovine rhodopsin (PDB#1F88) as a template. All 359 residues and two disulfide bonds in the rat AT1 receptor have been accounted for in this model. Ramachandran-map analysis and a 1 nanosecond molecular dynamics simulation of the solvated receptor with and without the bound ligand, Ang II, lend credence to the validity of the model. Docking calculations were performed with the agonist, Ang II and the antihypertensive antagonist, losartan. [Figure: see text].

Amino Acid Sequence↗

PubMed2000

Mechanism of calcite crystal growth inhibition by the N-terminal undecapeptide of lithostathine.

Pancreatic juice is supersaturated with calcium carbonate. Calcite crystals therefore may occur, obstruct pancreatic ducts, and finally cause a lithiasis. Human lithostathine, a protein synthesized by the pancreas, inhibits the growth of calcite crystals by inducing a habit modification: the rhombohedral (10 14) usual habit is transformed into a needle-like habit through the (11 0) crystal form. A similar observation was made with the N-terminal undecapeptide (pE(1)R(11)) of lithostathine. We therefore aimed at discovering how peptides inhibit calcium salt crystal growth. We solved the complete x-ray structure of lithostathine, including the flexible N-terminal domain, at 1.3 A. Docking studies of pE(1)R(11) with the (10 14) and (11 0) faces through molecular dynamics simulation resulted in three successive steps. First, the undecapeptide progressively unfolded as it approached the calcite surface. Second, mobile lateral chains of amino acids made hydrogen bonds with the calcite surface. Last, electrostatic bonds between calcium ions and peptide bonds stabilized and anchored pE(1)R(11) on the crystal surface. pE(1)R(11)-calcite interaction was stronger with the (11 0) face than with the (10 14) face, confirming earlier experimental observations. Energy contributions showed that the peptide backbone governed the binding more than did the lateral chains. The ability of peptides to inhibit crystal growth is therefore essentially based on backbone flexibility.

Amino Acid Sequence↗

PubMedDate not supplied

Human cytidine deaminase: understanding the catalytic mechanism.

In the absence of an experimentally elucidated three-dimensional structure of the human CDA, we built an homology model of this enzyme starting from the crystal structure of its E. coli homologous. Furthermore, we docked in the active site alternatively the substrate, the intermediate or the product. By means of molecular dynamics simulations, we determined the topology of the active site, identifying the amino acids involved in the catalytic mechanism, and outlining the central role played by E67.

Amino Acid Sequence↗

PubMed2002

New serotonin 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptor antagonists: synthesis, pharmacology, 3D-QSAR, and molecular modeling of (aminoalkyl)benzo and heterocycloalkanones.

A series of 52 conformationally constrained butyrophenones have been synthesized and pharmacologically tested as antagonists at 5-HT(2A), 5-HT(2B), and 5-HT(2C) serotonin receptors, useful for dissecting the role of each 5-HT(2) subtype in pathophysiology. These compounds were also a consistent set for the identification of structural features relevant to receptor recognition and subtype discrimination. Six compounds were found highly active (pK(i) > 8.76) and selective at the 5-HT(2A) receptor vs 5-HT(2B) and/or 5-HT(2C) receptors. Piperidine fragments confer high affinity at the 5-HT(2A) receptor subtype, with benzofuranone- and thiotetralonepiperidine as the most selective derivatives over 5-HT(2C) and 5-HT(2B) receptors, respectively; K(i) (2A/2C) and/or K(B) (2A/2B) ratios greater than 100 were obtained. Compounds showing a more pronounced selectivity at 5-HT(2A)/5-HT(2C) than at 5-HT(2A)/5-HT(2B) bear 6-fluorobenzisoxazolyl- and p-fluorobenzoylpiperidine moieties containing one methylene bridging the basic piperidine to the alkanone moiety. An ethylene bridge between the alkanone and the amino moieties led to ligands with higher affinities for the 5-HT(2B) receptor. Significant selectivity at the 5-HT(2B) receptor vs 5-HT(2C) was observed with 1-1[(1-oxo-1,2,3,4-tetrahydro-3-naphthyl)methyl]-4-[3-(p-fluorobenzoyl)propyl]piperazine (more than 100-fold higher). Although piperidine fragments also confer higher affinity at 5-HT(2C) receptors, only piperazine-containing ligands were selective over 5-HT(2A). Moderate selectivity was observed at 5-HT(2C) vs 5-HT(2B) (10-fold) with some compounds bearing a 4-[3-(6-fluorobenzisoxazolyl)]piperidine moiety in its structure. Molecular determinants for antagonists acting at 5-HT(2A) receptors were identified by 3D-QSAR (GRID-GOLPE) studies. Docking simulations at 5-HT(2A) and 5-HT(2C) receptors suggest a binding site for the studied type of antagonists (between transmembrane helices 2, 3, and 7) different to that of the natural agonist serotonin (between 3, 5, and 6).

Animals↗

PubMed2003

Nonequilibrium, multiple-timescale simulations of ligand-receptor interactions in structured protein systems.

Predicting the long-time, nonequilibrium dynamics of receptor-ligand interactions for structured proteins in a host fluid is a formidable task, but of great importance to predicting and analyzing cell-signaling processes and small molecule drug efficacies. Such processes take place on timescales on the order of milliseconds to seconds, so "brute-force" real-time, molecular or atomic simulations to determine absolute ligand-binding rates to receptor targets and over a statistical ensemble of systems are not currently feasible. In the current study, we implement on real protein systems a previously developed 3-5 hybrid molecular dynamics/Brownian dynamics algorithm, which takes advantage of the underlying, disparate timescales involved and overcomes the limitations of brute-force approaches. The algorithm is based on a multiple timescale analysis of the total system Hamiltonian, including all atomic and molecular structure information for the system: water, ligand, and receptor. In general, the method can account for the complex hydrodynamic, translational-orientational diffusion aspects of ligand-docking dynamics as well as predict the actual or absolute rates of ligand binding. To test some of the underlying features of the method, simulations were conducted here for an artificially constructed spherical protein "made" from the real protein insulin. Excellent comparisons of simulation calculations of the so-called grand particle friction tensor to analytical values were obtained for this system when protein charge effects were neglected. When protein charges were included, we found anomalous results caused by the alteration of the spatial, microscopic structure of water proximal to the protein surface. Protein charge effects were found to be highly significant and consistent with the recent hypothesis of Hoppert and Mayer (Am Sci 1999;87:518-525) for charged macromolecules in water, which involves the formation of a "water dense region" proximal to the charged protein surface followed by a "dilute water region." We further studied the algorithm on a D-peptide/HIV capside protein system and demonstrated the algorithms utility to study the nonequilibrium docking dynamics in this contemporary problem. In general, protein charge effects, which alter water structural properties in an anomalous fashion proximal to the protein surface, were found to be much more important than the so-called hydrodynamic interaction effects between ligand and receptor. The diminished role of hydrodynamic interactions in protein systems allows for a much simpler overall dynamic algorithm for the nonequilibrium protein-docking process. Further studies are now underway to critically examine this simpler overall algorithm in analyzing the nonequilibrium protein-docking problem.

Algorithms↗

PubMed1994

Molecular surface representations by sparse critical points.

We have defined a molecular surface representation that describes precisely and concisely the complete molecular surface. The representation consists of a limited number of critical points disposed at key locations over the surface. These points adequately represent the shape and the important characteristics of the surface, despite the fact that they are modest in number. We expect the representation to be useful in areas such as molecular recognition and visualization. In particular, using this representation, we are able to achieve accurate and efficient protein-protein and protein-small molecule docking.

Chymotrypsin↗