Amino Acid Side Chains In Water Research Articles

Simple physics-based analytical formulas for the potentials of mean force of the interaction of amino-acid side chains in water. VI. Oppositely charged side chains.

The two-site coarse-grained model for the interactions of charged side chains, to be used with our coarse-grained UNRES force field for protein simulations proposed in the accompanying paper, has been extended to pairs of oppositely charged side chains. The potentials of mean force of four pairs of molecules modeling charged amino-acid side chains, i.e., propionate-n-pentylamine cation (for aspartic acid-lysine), butyrate-n-pentylamine cation (for glutamic acid-lysine), propionate-1-butylguanidine (for aspartic acid-arginine), and butyrate-1-butylguanidine (for glutamic acid-arginine) pairs were determined by umbrella-sampling molecular dynamics simulations in explicit water as functions of distance and orientation, and the analytical expression was fitted to the potentials of mean force. Compared to pairs of like-charged side chains discussed in the accompanying paper, an average quadrupole-quadrupole interaction term had to be introduced to reproduce the Coulombic interactions, and a multistate model of charge distribution had to be introduced to fit the potentials of mean force of all oppositely charged pairs well. The model reproduces all salt-bridge minima and, consequently, is likely to improve the performance of the UNRES force field.

Simple physics-based analytical formulas for the potentials of mean force of the interaction of amino-acid side chains in water. V. Like-charged side chains.

A new model of side-chain-side-chain interactions for charged side-chains of amino acids, to be used in the UNRES force-field, has been developed, in which a side chain consists of a nonpolar and a charged site. The interaction energy between the nonpolar sites is composed of a Gay-Berne and a cavity term; the interaction energy between the charged sites consists of a Lennard-Jones term, a Coulombic term, a generalized-Born term, and a cavity term, while the interaction energy between the nonpolar and charged sites is composed of a Gay-Berne and a polarization term. We parametrized the energy function for the models of all six pairs of natural like-charged amino-acid side chains, namely propionate-propionate (for the aspartic acid-aspartic acid pair), butyrate-butyrate (for the glutamic acid-glutamic acid pair), propionate-butyrate (for the aspartic acid-glutamic acid pair), pentylamine cation-pentylamine cation (for the lysine-lysine pair), 1-butylguanidine cation-1-butylguanidine cation (for the arginine-arginine pair), and pentylamine cation-1-butylguanidine cation (for the lysine-arginine pair). By using umbrella-sampling molecular dynamics simulations in explicit TIP3P water, we determined the potentials of mean force of the above-mentioned pairs as functions of distance and orientation and fitted analytical expressions to them. The positions and depths of the contact minima and the positions and heights of the desolvation maxima, including their dependence on the orientation of the molecules were well represented by analytical expressions for all systems. The values of the parameters of all the energy components are physically reasonable, which justifies use of such potentials in coarse-grain protein-folding simulations.

Simple Physics-Based Analytical Formulas for the Potentials of Mean Force for the Interaction of Amino-Acid Side Chains in Water. 1. Approximate Expression for the Free Energy of Hydrophobic Association Based on a Gaussian-Overlap Model

Simple Physics-Based Analytical Formulas for the Potentials of Mean Force for the Interaction of Amino-Acid Side Chains in Water. 1. Approximate Expression for the Free Energy of Hydrophobic Association Based on a Gaussian-Overlap Model

Quantitative estimation of activities of mutant enzymes

A simple equation is presented for the prediction of catalytic efficiencies and Michaelis constants for pairs of mutant serine proteases and substrates with variable P1 side chains. The equation is a generalization of the “similis simili gaudet” principle formulated by Graf et al. [3] (Proc. Natl. Acad. Sci. U.S.A. 85 (1988) 4961, stating that in water amino-acid side chains with similar polarities tend to Interact stronger than dissimilar ones.