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M N Ponnuswamy

Publications and source records attributed to M N Ponnuswamy.

At least 19 recordsLinked to original sources
PubMed2006

Prediction of protein mutant stability using classification and regression tool.

Prediction of protein stability upon amino acid substitutions is an important problem in molecular biology and the solving of which would help for designing stable mutants. In this work, we have analyzed the stability of protein mutants using two different datasets of 1396 and 2204 mutants obtained from ProTherm database, respectively for free energy change due to thermal (DeltaDeltaG) and denaturant denaturations (DeltaDeltaG(H(2)O)). We have used a set of 48 physical, chemical energetic and conformational properties of amino acid residues and computed the difference of amino acid properties for each mutant in both sets of data. These differences in amino acid properties have been related to protein stability (DeltaDeltaG and DeltaDeltaG(H(2)O)) and are used to train with classification and regression tool for predicting the stability of protein mutants. Further, we have tested the method with 4 fold, 5 fold and 10 fold cross validation procedures. We found that the physical properties, shape and flexibility are important determinants of protein stability. The classification of mutants based on secondary structure (helix, strand, turn and coil) and solvent accessibility (buried, partially buried, partially exposed and exposed) distinguished the stabilizing/destabilizing mutants at an average accuracy of 81% and 80%, respectively for DeltaDeltaG and DeltaDeltaG(H(2)O). The correlation between the experimental and predicted stability change is 0.61 for DeltaDeltaG and 0.44 for DeltaDeltaG(H(2)O). Further, the free energy change due to the replacement of amino acid residue has been predicted within an average error of 1.08 kcal/mol and 1.37 kcal/mol for thermal and chemical denaturation, respectively. The relative importance of secondary structure and solvent accessibility, and the influence of the dataset on prediction of protein mutant stability have been discussed.

Amino Acid Substitution↗
PubMed2006

Crystal structure of haemoglobin from donkey (Equus asinus) at 3A resolution.

Haemoglobin from donkey was purified and crystallized in space group C2. The present donkey haemoglobin model comprises of two subunits alpha and beta. These alpha and beta subunits comprise of 141 and 146 amino acid residues, respectively, and the haem groups. The donkey haemoglobin differs from horse only in two amino acids of alpha-chain (His20 to Asn and Tyr24 to Phe) and these substitutions do not significantly change the secondary structural features of donkey haemoglobin. The haem group region and subunit contacts are closely resemble with that of horse methaemoglobin.

Amino Acid Sequence↗
PubMed2006

Average assignment method for predicting the stability of protein mutants.

Prediction of protein stability upon amino acid substitutions is an important problem in molecular biology and it will be helpful for designing stable mutants. In this work, we have analyzed the stability of protein mutants using three different data sets of 1791, 1396, and 2204 mutants, respectively, for thermal stability (DeltaTm), free energy change due to thermal (DeltaDeltaG), and denaturant denaturations (DeltaDeltaGH2O), obtained from the ProTherm database. We have classified the mutants into 380 possible substitutions and assigned the stability of each mutant using the information obtained with similar type of mutations. We observed that this assignment could distinguish the stabilizing and destabilizing mutants to an accuracy of 70-80% at different measures of stability. Further, we have classified the mutants based on secondary structure and solvent accessibility (ASA) and observed that the classification significantly improved the accuracy of prediction. The classification of mutants based on helix, strand, and coil distinguished the stabilizing/destabilizing mutants at an average accuracy of 82% and the correlation is 0.56; information about the location of residues at the interior, partially buried, and surface regions of a protein correctly identified the stabilizing/destabilizing residues at an average accuracy of 81% and the correlation is 0.59. The nine subclassifications based on three secondary structures and solvent accessibilities improved the accuracy of assigning stabilizing/destabilizing mutants to an accuracy of 84-89% for the three data sets. Further, the present method is able to predict the free energy change (DeltaDeltaG) upon mutations within a deviation of 0.64 kcal/mol. We suggest that this method could be used for predicting the stability of protein mutants.

Amino Acid Substitution↗
PubMed2005

Role of amino acid properties to determine backbone tau(N-Calpha-C') stretching angle in peptides and proteins.

The analysis of the basic geometry of amino acid residues of protein structures has demonstrated the invariability of all the bond lengths and bond angles except for tau, the backbone N-Calpha-C' angle. This angle can be widened or contracted significantly from the tetrahedral geometry to accommodate various other strains in the structure. In order to accurately determine the cause for this deviation, a survey is made for the tau angles using the peptide structures and the ultrahigh resolution protein structures. The average deviation of N-Calpha-C' angles from tetrahedral geometry for each amino acid in all the categories were calculated and then correlated with forty-eight physiochemical, energetic and conformational properties of amino acids. Linear and multiple regression analysis were carried out between the amino acid deviation and the 48 properties. This study confirms the deviation of tau angles in both the peptide and protein structures but similar forces do not influence them. The peptide structures are influenced by physical properties whereas as expected the conformational properties influence the protein structures. And it is not any single property that dominates the deviation but the combination of different factors contributes to the tau angle deviation.

Algorithms↗
PubMed2005

Relative importance of secondary structure and solvent accessibility to the stability of protein mutants. A case study with amino acid properties and energetics on T4 and human lysozymes.

Understanding the factors influencing the stability of protein mutants is an important task in molecular and computational biology. In this work, we have approached this problem by examining the relative importance of secondary structure and solvent accessibility of the mutant residue for understanding/predicting the stability of protein mutants. We have used hydrophobic, electrostatic and hydrogen bond free energy terms and nine unique physicochemical, energetic and conformational properties of amino acids in the present study and these parameters have been related with changes in thermal stability (DeltaTm) of all the single mutants of lysozymes based on single and multiple correlation coefficients. As expected the properties reflecting hydrophobicity and hydrophobic free energy play a major role to distinguish stabilizing and destabilizing mutants. The hydrophobic free energy due to carbon and nitrogen atoms distinguish the stability of coil and strand mutations to the accuracy of 100 and 90%, respectively. In agreement with previous results, the subgroup classification based on secondary structure and the information about its location in the structure yielded good relationship with the experimental DeltaTm. We revealed that the secondary structure information is equally or more important than solvent accessibility for understanding the stability of protein mutants. The comparison of amino acid properties with free-energy terms indicate that the energetic contribution explains the mutant stability better in coil region whereas the amino acid properties do better in strand region. Further, the combination of free energies with amino acid properties increased the correlation significantly. The present study demonstrates the importance of classifying the mutants based on secondary structure to the stability of proteins upon mutations.

Amino Acids↗
PubMed2005

Importance of main-chain hydrophobic free energy to the stability of thermophilic proteins.

Living organisms are found in the most unexpected places, including deep-sea vents at 100 degrees C and several hundred bars pressure, in hot springs. Needless to say, the proteins found in thermophilic species are much more stable than their mesophilic counterparts. There are no obvious reasons to say that one would be more stable than others. Even examination of the amino acids and comparison of structural features of thermophiles with mesophilies cannot bring satisfactory explanation for the thermal stability of such proteins. In order to bring out the hidden information behind the thermal stabilization of such proteins in terms of energy factors and their combinations, analysis were made on good resolution structures of thermophilic and their mesophilic homologous from 23 different families. From the structural coordinates, free energy contributions due to hydrophobic, electrostatic, hydrogen bonding, disulfide bonding and van der Waals interactions are computed. In this analysis, a vast majority of thermophilic proteins adopt slightly lower free energy contribution in each energy terms than its mesophilic counterparts. The major observation noted from this study is the lower hydrophobic free energy contribution due to carbon atoms and main-chain nitrogen atoms in all the thermophilic proteins. The possible combination of different free energy terms shows majority of the thermophilic proteins have lower free energy strategy than their mesophilic homologous. The derived results show that the hydrophobic free energy due to carbon and nitrogen atoms and such combinations of free energy components play a vital role in the thermostablisation of such proteins.

Animals↗
PubMed2004

Role of non-covalent interactions for determining the folding rate of two-state proteins.

Understanding the factors influencing the folding rate of proteins is a challenging problem. In this work, we have analyzed the role of non-covalent interactions for the folding rate of two-state proteins by free-energy approach. We have computed the free-energy terms, hydrophobic, electrostatic, hydrogen-bonding and van der Waals free energies. The hydrophobic free energy has been divided into the contributions from different atoms, carbon, neutral nitrogen and oxygen, charged nitrogen and oxygen, and sulfur. All the free-energy terms have been related with the folding rates of 28 two-state proteins with single and multiple correlation coefficients. We found that the hydrophobic free energy due to carbon atoms and hydrogen-bonding free energy play important roles to determine the folding rate in combination with other free energies. The normalized energies with total number of residues showed better results than the total energy of the protein. The comparison of amino acid properties with free-energy terms indicates that the energetic terms explain better the folding rate than amino acid properties. Further, the combination of free energies with topological parameters yielded the correlation of 0.91. The present study demonstrates the importance of topology for determining the folding rate of two-state proteins.

Binding Sites↗
PubMed2004

Purification and crystallization of haemoglobin from donkey (Equus asinus).

Haemoglobin acts as an important protein for oxygen carrier in all living beings. Purification of donkey haemoglobin was done using PEG 4000 as a separating medium. Crystallization was achieved using hanging drop vapor diffusion method using 2.8 M phosphate buffer, pH 6.8. Data collection was done using mar345 image plate detector system. The crystals grown under 2.8 M phosphate buffer are monoclinic with space group C2 and cell dimensions a=107.664 A, b=63.084 A, c=54.042 A, and beta=111.747 degrees.

Animals↗
PubMed2003

t-3-Isopropyl-1-methyl-r-2,c-6-diphenylpiperidin-4-one thiosemicarbazone.

The piperidine ring in the title compound, C(22)H(28)N(4)S, exhibits a chair conformation. The thiosemicarbazone moiety adopts an extended conformation, and the planar phenyl rings are oriented equatorially with respect to the piperidine ring. Two intermolecular hydrogen bonds involving the S atom form molecular pairs, and the crystal structure is stabilized by weak C-H.pi interactions in addition to van der Waals forces.

Journal Article↗
PubMed2002

Purification and crystallization of coconut globulin cocosin from Cocos nucifera.

Cocosin is a legume class reserve protein found in coconut endosperm. Using coconut endosperm, two methods of purification were done. Crystallization was achieved by vapor diffusion (hanging drop) method using MPD, PEG 3350 and PEG 4000 as precipitants. X-ray diffraction data to 3.5-A resolution were collected using Mar345 image plate detector system. Crystals of cocosin grown under 20% MPD, are rhombohedral with space group R3 and cell dimensions a=92.829 A, b=92.829 A, c=215.290 A.

Cocos↗
PubMed2002

9,9-Dimethoxy-7,11-diphenyl-2,4-diazaspiro[5.5]undecane-1,3,5-trione monohydrate.

Due to steric repulsions, the cyclohexane ring in the title compound, C(23)H(24)N(2)O(5).H(2)O, shows some bond-length abnormalities and adopts a chair conformation. The pyrimidine and cyclohexane rings are approximately perpendicular to each other, and the phenyl rings are equatorial. C-H.pi and N-H.O intermolecular interactions, as well as C-H.O inter- and intramolecular interactions, occur between the molecules. In addition to van der Waals interactions, the water molecule interacts with the pyrimidinetrione ring to stabilize the structure.

Journal Article↗
PubMed2001

4-[3-(3,4-dimethoxyphenyl)prop-2-enoyl]phenyl methacrylate and 4-[3-(2-bromophenyl)prop-2-enoyl]phenyl methacrylate.

Chalcones (alpha,beta-unsaturated ketones) are effective antitumour agents. It has been proved that having halogen or methoxy groups substituted in various positions of the phenyl ring enhances the activity of chalcones many times. The title compounds, C21H20O5 and C19H15BrO3, respectively, were chosen for crystallographic study in order to determine their structures and conformations. In both compounds, the keto group is in the s-cis conformation and is almost planar. There are weak intramolecular interactions in both structures.

Antineoplastic Agents↗
PubMed2001

Distribution of amino acid residues and residue-residue contacts in molecular chaperones.

The amino acid distribution and residue-residue contacts in molecular chaperones are different when compared to normal globular proteins. The study of molecular chaperones reveals a different surrounding environment to exist for the residues Cys, Trp, and His which may play an important role in determining the chaperone structures. Unlike globular proteins, it has been observed that a one-to-one correspondence between the amino acid distribution in a sequence and the structures of molecular chaperones. The preference of amino acid residues surrounding all 20 types of residues in secondary structures and their accessible surface areas have been analysed.

Amino Acids↗
PubMed2000

Structural class prediction: an application of residue distribution along the sequence.

Deciphering the native conformation of proteins from their amino acid sequences is one of the most challenging problems in molecular biology. Information on the secondary structure of a protein can be helpful in understanding its native folded state. In our earlier work on molecular chaperones, we have analyzed the hydrophobic and charged patches, short-, medium- and long-range contacts and residue distributions along the sequence. In this article, we have made an attempt to predict the structural class of globular and chaperone proteins based on the information obtained from residue distributions. This method predicts the structural class with an accuracy of 93 and 96%, respectively, for the four- and three-state models in a training set of 120 globular proteins, and 90 and 96%, respectively, for a test set of 80 proteins. We have used this information and methodology to predict the structural classes of chaperones. Interestingly most of the chaperone proteins are predicted under alpha/beta or mixed folding type.

Amino Acid Sequence↗
PubMed1998

Analysis of hydrophobic and charged patches and influence of medium- and long-range interactions in molecular chaperones.

The amino acid composition of the aromatic residues Phe, Tyr and Trp are much less significant in chaperones and the residues Cys, Glu, His, Met and Pro vary significantly in chaperones compared to normal globular proteins. In the present work, we have analysed the hydrophobic and charged patches in molecular chaperones which provide more insight for a better understanding of chaperone folding. Also, we have investigated the role of medium- and long-range contacts in chaperones and the preference of amino acid residues influenced by these interactions. Furthermore, the role of hydrophobic and helix-forming residues and disulfide bonding in these interactions have been discussed.

Amino Acids↗
PubMed1998

Solvent accessibility analysis on the mutants of Hsc70 ATPase fragment.

Molecular chaperones are the cellular proteins which mediate the correct folding of other polypeptides. The concept of 'solvent accessibility' is one of the most powerful tools to understand the structure and stability of protein molecules. The hydrophobic variation of amino acid residues due to point mutations at many active sites of chaperone protein Hsc70 using solvent accessibility analysis is carried out. The numerical indices for several properties of amino acid residues, such as, reduction in accessibility, preference of amino acid residues in interior and surface parts, transfer free energy and the preference of amino acid residues to change their positions (buried/exposed) due to amino acid substitutions for Hsc70 and its mutants were set up. The accessibility of amino acid residues varies much between native and mutant proteins whereas there is no major changes on their conformations. The conformational stability for Hsc70 and its mutants were established and the computed hydrophobic free energy change is around 10 kcal/mol due to single amino acid substitution.

HSP70 Heat-Shock Proteins↗
PubMed1989

Structure of antischistosome compounds. V 1,6-Hexanediylbis(triphenylphosphonium) dibromide.

C42H42P2(2+).2Br-, Mr = 768.6, triclinic, P1, a = 13.328 (2), b = 23.110 (3), c = 9.417 (1) A, alpha = 90.75 (1), beta = 109.62 (1), gamma = 91.23 (1) degrees, V = 2730.86 A3, Z = 3, Dx = 1.402 g cm3, graphite-monochromatized Cu K alpha radiation, lambda = 1.5418 A, mu = 52.0 cm-1, F(000) = 1182, T = 292 K. Final R = 0.051 for 5225 reflections with I greater than 3 sigma (I). Structure solved by Patterson methods and delta F syntheses. One molecule is located at the center of symmetry of the unit cell. The hexane moieties of all three molecules are in the trans extended conformation. However, one of the P-C-C-C torsion angles in the complete molecule in the asymmetric unit is 118.4 (6) degrees, the corresponding P-C-C-C torsion angle about the other P atom being 178.7 (5) degrees. This creates a conformational asymmetry in an otherwise symmetric molecule. This conformation permits the formation of a nearly square, planar, noncovalent interaction involving this P atom with one of the Br- ions and a symmetry-related Br--P interaction. The remaining P atoms and Br- ions are noncovalently linked to this square, approximately along the alpha axis. This noncovalent network is nearly parallel to the [011] plane, but does not extend beyond the [020] and [020] planes. The half-molecule in the asymmetric unit is approximately 45 degrees to the whole molecule, with two of its phenyl rings directed toward and perpendicular to one of the phenyl rings of the asymmetric triphenylphosphonium group of the whole molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallization↗