A connection rule for [formula omitted]-carbon coarse-grained elastic network models using chemical bond information

Abstract

A sparser but more efficient connection rule (called a bond-cutoff method) for a simplified α -carbon coarse-grained elastic network model is presented. One of conventional connection rules for elastic network models is the distance-cutoff method, where virtual springs connect an α -carbon with all neighbor α -carbons within predefined distance-cutoff value. However, though the maximum interaction distance between α -carbons is reported as 7Å, this cutoff value can make the elastic network unstable in many cases of protein structures. Thus, a larger cutoff value (>11Å) is often used to establish a stable elastic network model in previous researches. To overcome this problem, a connection rule for backbone model is proposed, which satisfies the minimum condition to stabilize an elastic network. Based on the backbone connections, each type of chemical interactions is considered and added to the elastic network model: disulfide bonds, hydrogen bonds, and salt-bridges. In addition, the van der Waals forces between α -carbons are modeled by using the distance-cutoff method. With the proposed connection rule, one can make an elastic network model with less than 7Å distance cutoff, which can reveal protein flexibility more sharply. Moreover, the normal modes from the new elastic network model can reflect conformational changes of a given protein better than ones by the distance-cutoff method. This method can save the computational cost when calculating normal modes of a given protein structure, because it can reduce the total number of connections. As a validation, six example proteins are tested. Computational times and the overlap values between the conformational change and infinitesimal motion calculated by normal mode analysis are presented. Those animations are also available at UMass Morph Server ( http://biomechanics.ecs.umass.edu/umms.html).