Modeling solvent effects in molecular dynamics simulations of proteins

Abstract

A series of computer simulations has been carried out on bovine pancreatic trypsin inhibitor using various models to mimic the effects of explicit bulk solvent on the structure of the protein.The solvent properties included are the polarization of the solute by the polar bulk solvent and the restraining effect on the motional freedom of the solute due to frictional drag at the solventprotein surface interface. The former has been included by using a distance-dependent dielectric permittivity to screen the electrostatic interactions, whereas the latter is simulated by adding a limited number of solvent molecules near the protein surface. To achieve the proper mobility of the water molecules, their motion was restrained by adding a harmonic restraining force. It was found that a very small force constant was sufficient to model the static and dynamical behavior of the fully solvated solute, but that it was necessary to include enough explicit waters to occupy the first solvation shell. 8

Improvement of side-chain modeling in proteins with the self-consistent mean field theory method based on an analysis of the factors influencing prediction

“…We used two different forms of the dielectric constant: a constant dielectric constant of 15 and a distance-dependent dielectric constant described by Solmajer and Mehler 34,35 defined by…”

Computer-aided drug design: A free energy perturbation study on the binding of methyl-substituted pterins and N5-deazapterins to dihydrofolate reductase

“…Boundary effects would be practically eliminated by solvating the protein and constructing the NTP (or NTV) ensembles consistently for each of the simulations. It may be necessary to perform calculations on more fully solvated protein systems, at additional computational expense, or to explore the use of more computationally efficient models which take into account the effects of solvent on electrostatic interactions and protein dynamics [52,53]. There are also other possible sources of error, such as the force fields, and the assumed binding geometry.…”

Solvent effects in active-site molecular dynamics simulations on the binding of 8-methyl-N5-deazapterin and 8-methylpterin to dihydrofolate reductase

“…22 In addition to overall rms deviations, we computed rms deviations with re- spect to the secondary structure elements given in Table 11. The solvent numbers are given for the first hydration shell in the initially solvated complexes as an indication of the overall solvent accessibility of each element.…”

“…Hoyever, including the first hydration shell (of 3-A thickness) ip the simulation, a value of k = 0.005 kcal/mol/A2 was found to give better results. 22 We have tested values of k = 25, 2.5, and 0.005 in the present work on the active-site MD of DHFR.…”