Peptide and protein folding and conformational equilibria: theoretical treatment of electrostatics and hydrogen bonding with implicit solvent models.
Since biomolecules exist in aqueous and membrane environments, the accurate modeling of solvation, and hydrogen bonding interactions in particular, is essential for the exploration of structure and function in theoretical and computational studies. In this chapter, we focus on alternatives to explicit solvent models and discuss recent advances in generalized Born (GB) implicit solvent theories. We present a brief review of the successes and shortcomings of the application of these theories to biomolecular problems that are strongly linked to backbone H-bonding and electrostatics. This discussion naturally leads us to explore existing areas for improvement in current GB theories and our approach towards addressing a number of the key issues that remain in the refinement of these models. Specifically, the critical importance of balancing solvation forces and intramolecular forces in GB models is illustrated by examining the influence of backbone hydrogen bond strength and backbone dihedral energetics on conformational equilibria of small peptids.
Department of Molecular Biology and Center for Theoretical Biological Physics, The Scripps Research Institute, La Jolla, California 92037.
Wonpil
W
Im
Jianhan
J
Chen
Charles L
CL
Brooks
D003198:Computer Simulation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008962:Models, Theoretical; D010455:Peptides; D017510:Protein Folding; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics
D010455:Peptides; D012997:Solvents