Virtual Quantification of Protein Stability Using Applied Kinetic and Thermodynamic Parameters

S. Prasanth Kumar, Muthusamy Meenatchi


Protein stability, the most important aspect of molecular dynamics and simulations, requires sophisticated instrumentations of molecular biology to analyze its kinetic and thermodynamic background. Sequence- and structure-based programs on protein stability exist which relies only on single point mutations and sequence optimality. The energy distribution conferred by each hydrophobic amino acid in the protein essentially paves way for understanding its stability. To the best of our knowledge, Protein Stability is a first program of its kind, developed to explore the energy requirement of each amino acid in the protein sequence derived from various applied kinetic and thermodynamic quantities. The algorithm is strongly dependent both on kinetic quantities such as atomic solvation energies and solvent accessible surface area and thermodynamic quantities viz. enthalpy, entropy, heat capacity, etc. The hydrophobicity pattern of protein was considered as the important component of protein stabilization.


Molecular modeling; kinetics; thermodynamics; protein stability; hydrophobicity

Full Text:



Albert T, Dao-pin S, Nye JA, Muchmore DC, Matthews BW (1987) Temperature-sensitive mutations of bacteriophage T4 lysoszyme occur at sites of low mobility and low solvent accessibility in the folded protein. Biochemistry, 26: 3754-3758.

Baldwin RL (1986) Temperature dependence of the hydrophobic interaction in protein folding. Proceeding of the National Academy of Sciences, 83: 8069-8072.

Bordo D, Argos P (1991) Suggestions for “safe” residue substitutions in site-directed mutagensis. Journal of Molecular Biology, 217: 721-729.

Capriotti E, Fariselli P, Casadio, R (2005) I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure. NAR, 33: 306–310.

Dehouck Y, Kwasigroch JM, Gilis D, Rooman M. [2011] PoPMuSiC 2.1: a web server for the estimation of protein stability changes upon mutation and sequence optimality. BMC Bioinformatics, 12: 151-167.

Eisenberg D, McLachlan AD (1986) Solvation energy in protein folding and binding. Nature, 319: 199-203.

Erikkson AE, Basse WA, Zhang XJ, Heinz DW, Blaber M, Baldwin EP, Matthews BW. (1992) Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. Science, 255: 178-183

Herzfeld J (1991) Understanding hydrophobic behaviour. Science, 253: 88-92.

Him HJ, Steif C, Vogl T, Meyer R, Renner M, Ledermiillers R (1993) Fundamentals of protein stability. Pure & Applied Chemistry, 65: 947-952.

Juffer AH, Eisenhaber F, Hubbard SJ, Walther D, Argos P (1995) Comparison of atomic solvation parametric sets: applicability and limitations in protein folding and binding. Protein Science, 4: 2499-2509.

Lins L, Brasseur, R (1995) The hydrophobic effect in protein folding. FASEB, 9: 535-540.

Matthews BW (1993) Structural and genetic analysis of protein stability. Annual Reviews of Biochemistry, 62: 139-160.

Parthiban V, Gromiha MM, Schomburg D (2006) CUPSAT: prediction of protein stability upon point mutations. NAR, 34: 239–242.

Perutz MF, Raidt H (1975) Stereochemical basis of heat stability in bacterial ferredoxins and in haemoglobin A2. Nature, 255: 256-259.

Schymkowitz J, Borg J, Stricher F, Nys R, Rousseau F, Serrano L (2005) The FoldX web server: an online force field. NAR, 33: 382–388.

Taneja S, Ahmad F (1994) Increased thermal stability of proteins in the presence of amino acids. Journal of Biochemistry, 303: 147-153.

Tisdall J (2001) Beginning Perl for Bioinformatics. O'Reilly Publications, New York.

Wesson L, Eisenberg D (1992) Atomic solvation parameters applied to molecular dynamics of proteins in solution. Protein Science, 1: 227-235.

Wimley WC, Creamer TP, White SH (1996) Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides. Journal of Biochemistry, 35: 5109-5124.

Wolfenden R, Andersson L, Cullis P, Southgate C (1981) Affinities of amino acid side chains for solvent water. Journal of Biochemistry, 20: 849-855.



  • There are currently no refbacks.

Copyright (c)