Gaussian network model can be enhanced by combining solvent accessibility in proteins

Abstract

Abstract Gaussian network model (GNM), regarded as the simplest and most representative coarse-grained model, has been widely adopted to analyze and reveal protein dynamics and functions. Designing a variation of the classical GNM, by defining a new Kirchhoff matrix, is the way to improve the residue flexibility modeling. We combined information arising from local relative solvent accessibility (RSA) between two residues into the Kirchhoff matrix of the parameter-free GNM. The undetermined parameters in the new Kirchhoff matrix were estimated by using particle swarm optimization. The usage of RSA was motivated by the fact that our previous work using RSA based linear regression model resulted out higher prediction quality of the residue flexibility when compared with the classical GNM and the parameter free GNM. Computational experiments, conducted based on one training dataset, two independent datasets and one additional small set derived by molecular dynamics simulations, demonstrated that the average correlation coefficients of the proposed RSA based parameter-free GNM, called RpfGNM, were significantly increased when compared with the parameter-free GNM. Our empirical results indicated that a variation of the classical GNMs by combining other protein structural properties is an attractive way to improve the quality of flexibility modeling.