Empirical potentials and functions for protein folding and binding.
Simplified models and empirical potentials are being increasingly used for the analysis of proteins, frequently augmenting or replacing molecular mechanics approaches. Recent folding simulations have employed potentials that, in addition to terms assuring proper polypeptide geometry, include only two noncovalent effects-hydrogen bonding and hydrophobicity, with extremely simple approximations to the latter. The potentials that have been used in the free-energy ranking of protein-ligand complexes have generally been more involved. These potentials have more detailed solvation models and account for both local (hydrophobic and polar) solute-solvent phenomena and long range electrostatic solvation effects. The models of solvation that have been used most frequently are surface area related atomic parameters, knowledge-based models extracted from protein-structure data, and continum electrostatics with an additional area-related parameter. The knowledge-based approaches to solvation, although convenient and accurate enough, are suspect of double counting certain free-energy terms.
Vajda
S
S
Department of Biomedical Engineering, Boston University, 44 Cummington St, Boston, MA 02215, USA. vajda@enga.bu.edu
Sippl
M
M
Novotny
J
J
D016208:Databases, Factual; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics