Biomedical subjects

Seung-Yeon Kim

Publications and source records attributed to Seung-Yeon Kim.

15 recordsLinked to original sources

PubMed2006

Protein folding using fragment assembly and physical energy function.

We perform a systematic study of the effects of sequence-independent backbone interactions and sequence-dependent side-chain interactions on protein folding using fragment assembly and physical energy function. Structures for ten proteins belonging to various structural classes are predicted only with Lennard-Jones interaction between backbone atoms. We find nativelike structures for beta proteins, suggesting that for proteins in this class, the global tertiary structures can be determined mainly by sequence-independent backbone interactions. On the other hand, for alpha proteins, nonlocal hydrophobic side-chain interaction is also required to obtain nativelike structures.

Computer Simulation↗

PubMed2006

Density of Yang-Lee zeros for the Ising ferromagnet.

The densities of Yang-Lee zeros for the Ising ferromagnet on the L x L square lattice are evaluated from the exact grand partition functions (L=3 approximately 16). The properties of the density of Yang-Lee zeros are discussed as a function of temperature T and system size L. The three different classes of phase transitions for the Ising ferromagnet--first-order phase transition, second-order phase transition, and Yang-Lee edge singularity--are clearly distinguished by estimating the magnetic scaling exponent yh from the densities of zeros for finite-size systems. The divergence of the density of zeros at Yang-Lee edge in high temperatures (Yang-Lee edge singularity), which has been detected only by the series expansion until now for the square-lattice Ising ferromagnet, is obtained from the finite-size data. The identification of the orders of phase transitions in small systems is also discussed using the density of Yang-Lee zeros.

Journal Article↗

PubMed2006

Application of the multiensemble sampling to the equilibrium folding of proteins.

MOTIVATION: Conventional Monte Carlo and molecular dynamics simulations of proteins in the canonical ensemble are of little use, because they tend to get trapped in states of energy local minima at low temperatures. One way to surmount this difficulty is to use a non-Boltzmann sampling method in which conformations are sampled upon a general weighting function instead of the conventional Boltzmann weighting function. The multiensemble sampling (MES) method is a non-Boltzmann sampling method that was originally developed to estimate free energy differences between systems with different potential energies and/or at different thermodynamic states. The method has not yet been applied to studies of complex molecular systems such as proteins. RESULTS: MES Monte Carlo simulations of small proteins have been carried out using a united-residue force field. The proteins at several temperatures from the unfolded to the folded states were simulated in a single MC run at a time and their equilibrium thermodynamic properties were calculated correctly. The distributions of sampled conformations clearly indicate that, when going through states of energy local minima, the MES simulation did not get trapped in them but escaped from them so quickly that all the relevant parts of conformation space could be sampled properly. A two-step folding process consisting of a collapse transition followed by a folding transition is observed. This study demonstrates that the use of MES alleviates the multiple-minima problem greatly. AVAILABILITY: Available on request from the authors.

Algorithms↗

PubMed2005

Structure optimization by conformational space annealing in an off-lattice protein model.

The optimization results by conformational space annealing are presented for an off-lattice protein model consisting of hydrophobic and hydrophilic residues in Fibonacci sequences. The ground-state energies found are lower than those reported in the literature. In addition, the ground-state conformations in three dimensions exhibit the important aspect of forming a single hydrophobic core in real proteins. The energy landscape for the population of local minima is also investigated.

Algorithms↗

PubMed2005

PPRODO: prediction of protein domain boundaries using neural networks.

Successful prediction of protein domain boundaries provides valuable information not only for the computational structure prediction of multidomain proteins but also for the experimental structure determination. Since protein sequences of multiple domains may contain much information regarding evolutionary processes such as gene-exon shuffling, this information can be detected by analyzing the position-specific scoring matrix (PSSM) generated by PSI-BLAST. We have presented a method, PPRODO (Prediction of PROtein DOmain boundaries) that predicts domain boundaries of proteins from sequence information by a neural network. The network is trained and tested using the values obtained from the PSSM generated by PSI-BLAST. A 10-fold cross-validation technique is performed to obtain the parameters of neural networks using a nonredundant set of 522 proteins containing 2 contiguous domains. PPRODO provides good and consistent results for the prediction of domain boundaries, with accuracy of about 66% using the +/-20 residue criterion. The PPRODO source code, as well as all data sets used in this work, are available from http://gene.kias.re.kr/ approximately jlee/pprodo/.

Amino Acids↗

PubMed2005

Prediction of protein solvent accessibility using fuzzy k-nearest neighbor method.

MOTIVATION: The solvent accessibility of amino acid residues plays an important role in tertiary structure prediction, especially in the absence of significant sequence similarity of a query protein to those with known structures. The prediction of solvent accessibility is less accurate than secondary structure prediction in spite of improvements in recent researches. The k-nearest neighbor method, a simple but powerful classification algorithm, has never been applied to the prediction of solvent accessibility, although it has been used frequently for the classification of biological and medical data. RESULTS: We applied the fuzzy k-nearest neighbor method to the solvent accessibility prediction, using PSI-BLAST profiles as feature vectors, and achieved high prediction accuracies. With leave-one-out cross-validation on the ASTRAL SCOP reference dataset constructed by sequence clustering, our method achieved 64.1% accuracy for a 3-state (buried/intermediate/exposed) prediction (thresholds of 9% for buried/intermediate and 36% for intermediate/exposed) and 86.7, 82.0, 79.0 and 78.5% accuracies for 2-state (buried/exposed) predictions (thresholds of each 0, 5, 16 and 25% for buried/exposed), respectively. Our method also showed slightly better accuracies than other methods by about 2-5% on the RS126 dataset and a benchmarking dataset with 229 proteins. AVAILABILITY: Program and datasets are available at http://biocom1.ssu.ac.kr/FKNNacc/ CONTACT: jul@ssu.ac.kr.

Algorithms↗

PubMed2005

An efficient molecular docking using conformational space annealing.

Molecular docking falls into the general category of global optimization problems because its main purpose is to find the most stable complex consisting of a receptor and its ligand. Conformational space annealing (CSA), a powerful global optimization method, is incorporated with the Tinker molecular modeling package to perform molecular docking simulations of six receptor-ligand complexes (3PTB, 1ULB, 2CPP, 1STP, 3CPA, and 1PPH) from the Protein Data Bank. In parallel, Monte Carlo with the minimization (MCM) method is also incorporated into the Tinker package for comparison. The energy function, consisting of electrostatic interactions, van der Waals interactions, and torsional energy terms, is calculated using the AMBER94 all-atom empirical force field. Rigid docking simulations for all six complexes and flexible docking simulations for three complexes (1STP, 3CPA, and 1PPH) are carried out using the CSA and the MCM methods. The simulation results show that the docking procedures using the CSA method generally find the most stable complexes as well as the native-like complexes more efficiently and accurately than those using the MCM, demonstrating that CSA is a promising search method for molecular docking problems.

Algorithms↗

PubMed2005

Understanding the structural characteristics of compstatin by conformational space annealing.

The structural characteristics of the 13-residue compstatin molecule are investigated using the conformational space annealing (CSA) method with CHARMM force field and the GBSA continuum solvent model. In order to sample conformations in the energy range of the minimized NMR structures, we have used the stopping criterion to the CSA search when a conformation whose energy is less than -490 kcal/mol is found. With this stopping criterion, a great variety of conformations are generated around experimentally known structures. Twenty independent CSA runs starting from random states find 1000 representative conformations in the energy landscape of the compstatin, which are classified into thirty-one structural families. The majority of the conformations (94.4%) are in the coil state. Other conformers containing a 3(10)-helix, a pi-helix, a beta-hairpin, and an alpha-helix are also found.

Models, Molecular↗

PubMed2005

Fisher zeros of the Ising antiferromagnet in an arbitrary nonzero magnetic field.

From the exact partition functions of the Ising model on L x L square lattices (up to L = 14) in an arbitrary nonzero external magnetic field H, the precise distributions of the Fisher zeros in the complex temperature (a = e(2betaJ)) plane are obtained. Our results indicate that in the limit L-->infinity the Fisher zeros for H not = 0 do cut the positive real axis at the antiferromagnetic critical point ac(H); these values are compared with the results of closed-form approximations for the antiferromagnetic critical line. From the Fisher zeros the thermal scaling exponent yt = 1 is also obtained along the critical line, indicating the logarithmic singularity of the specific heat for the antiferromagnetic Ising model even in a strong uniform magnetic field.

Journal Article↗

PubMed2005

Folding simulations of small proteins.

Understanding how a protein folds is a long-standing challenge in modern science. We have used an optimized atomistic model (united-residue force field) to simulate folding of small proteins of various structures: HP-36 (alpha protein), protein A (beta), 1fsd (alpha+beta), and betanova (beta). Extensive Monte Carlo folding simulations (ten independent runs with 10(9) Monte Carlo steps at a temperature) starting from non-native conformations are carried out for each protein. In all cases, proteins fold into their native-like conformations at appropriate temperatures, and glassy transitions occur at low temperatures. To investigate early folding trajectories, 200 independent runs with 10(6) Monte Carlo steps are also performed at a fixed temperature for a protein. There are a variety of possible pathways during non-equilibrium early processes (fast process, approximately 10(4) Monte Carlo steps). Finally, these pathways converge to the point unique for each protein. The convergence point of the early folding pathways can be determined only by direct folding simulations. The free energy surface, an equilibrium thermodynamic property, dictates the rest of the folding (slow process, approximately 10(8) Monte Carlo steps).

Computer Simulation↗

PubMed2005

Protein structure prediction based on fragment assembly and parameter optimization.

We propose a novel method for ab-initio prediction of protein tertiary structures based on the fragment assembly and global optimization. Fifteen residue long fragment libraries are constructed using the secondary structure prediction method PREDICT, and fragments in these libraries are assembled to generate full-length chains of a query protein. Tertiary structures of 50 to 100 conformations are obtained by minimizing an energy function for proteins, using the conformational space annealing method that enables one to sample diverse low-lying local minima of the energy. Then in order to enhance the performance of the prediction method, we optimize the linear parameters of the energy function, so that the native-like conformations become energetically more favorable than the non-native ones for proteins with known structures. We test the feasibility of the parameter optimization procedure by applying it to the training set consisting of three proteins: the 10-55 residue fragment of staphylococcal protein A (PDB ID 1bdd), a designed protein betanova, and 1fsd.

Models, Molecular↗

PubMed2004

Yang-Lee zeros of the antiferromagnetic Ising model.

There exists the famous circle theorem on the Yang-Lee zeros of the ferromagnetic Ising model. However, the Yang-Lee zeros of the antiferromagnetic Ising model are much less well understood than those of the ferromagnetic model. The precise distribution of the Yang-Lee zeros of the antiferromagnetic Ising model only with nearest-neighbor interaction J on LxL square lattices is determined as a function of temperature a=e(2betaJ) (J<0), and its relation to the phase transitions is investigated. In the thermodynamic limit (L-->infinity), the distribution of the Yang-Lee zeros of the antiferromagnetic Ising model cuts the positive real axis in the complex x=e(-2betaH) plane, resulting in the critical magnetic field +/-H(c)(a), where H(c)>0 below the critical temperature a(c)=square root of 2-1. The results suggest that the value of the scaling exponent y(h) is 1 along the critical line for a<a(c).

Journal Article↗

PubMed2004

Prediction of protein tertiary structure using PROFESY, a novel method based on fragment assembly and conformational space annealing.

A novel method for ab initio prediction of protein tertiary structures, PROFESY (PROFile Enumerating SYstem), is proposed. This method utilizes the secondary structure prediction information of a query sequence and the fragment assembly procedure based on global optimization. Fifteen-residue-long fragment libraries are constructed using the secondary structure prediction method PREDICT, and fragments in these libraries are assembled to generate full-length chains of a query protein. Tertiary structures of 50 to 100 conformations are obtained by minimizing an energy function for proteins, using the conformational space annealing method that enables one to sample diverse low-lying local minima of the energy. We apply PROFESY for benchmark tests to proteins with known structures to demonstrate its feasibility. In addition, we participated in CASP5 and applied PROFESY to four new-fold targets for blind prediction. The results are quite promising, despite the fact that PROFESY was in its early stages of development. In particular, PROFESY successfully provided us the best model-one structure for the target T0161.

Caspases↗

PubMed2004

Density of the Fisher zeros for the three-state and four-state Potts models.

The numbers of states up to L=12 for the three-state Potts model and up to L=10 for the four-state Potts model on LxL square lattice with self-dual boundary condition are enumerated using the microcanonical transfer matrix exploiting the permutation symmetry of the model. From these numbers of states, the densities of the Fisher zeros g(theta) of the partition function in the complex u=(1+(Q-1) e(-betaJ) )/square root[Q] plane are determined for the zeros on the unit circle u(0) = e(itheta). For small theta the density of zeros obeys the finite-size scaling, allowing us to estimate the order parameter and the thermal exponent.

Journal Article↗

PubMed2004

Folding of small proteins using a single continuous potential.

Extensive Monte Carlo folding simulations for four proteins of various structural classes are carried out, using a single continuous potential (united-residue force field). In all cases, collapse occurs at a very early stage, and proteins fold into their nativelike conformations at appropriate temperatures. We also observe that glassy transitions occur at low temperatures. The simulation results demonstrate that the folding mechanism is controlled not only by thermodynamic factors but also by kinetic factors: The way a protein folds into its native structure is also determined by the convergence point of early folding trajectories, which cannot be obtained by the free energy surface.

Biophysics↗