An Artificial Neural Network Based Approach for Identification of Native Protein Structures Using an Extended Forcefield

Abstract

Current protein forcefields like the ones seen in CHARMM or Xplor-NIH have many terms that include bonded and non-bonded terms. Yet the forcefields do not take into account the use of hydrogen bonds which are important for secondary structure creation and stabilization of proteins. SCOPE is an open-source program that generates proteins from rotamer space. It then creates a forcefield that uses only non-bonded and hydrogen bond energy terms to create a profile for a given protein. The profiles can then be used in an artificial neural network to create a linear model which is funneled to the true protein conformation.

Dynafold: A Dynamic Programming Approach to Protein Backbone Structure Determination From Minimal Sets of Residual Dipolar Couplings

“…However, since protein structures are required to conform to an accepted model of peptide geometry, its structural parameterization can be described more succinctly. Parameterization of protein structure in terms of its dihedral angles 40,64,65 would lead to a significant reduction of the search variables and therefore, improved computation time. When limiting the scope of structure determination to the backbone atoms represented in the rotamer-space reduces the set of parameters to the φ and ψ backbone torsion angles.…”

An artificial neural network approach to improving the correlation between protein energetics and the backbone structure

“…Furthermore, consecutive hydrogen bonds have been shown to exhibit a cooperativity phenomenon, where the total potential energy is greater than the sum of its individual components . This has motivated the explicit calculation of hydrogen bonds within SCOPE , as well as other approaches . Our implementation of SCOPE's hydrogen bond calculation, the details of which have been published previously , is designed specifically to be consistent with that of the DSSP program .…”

“…This has motivated the explicit calculation of hydrogen bonds within SCOPE , as well as other approaches . Our implementation of SCOPE's hydrogen bond calculation, the details of which have been published previously , is designed specifically to be consistent with that of the DSSP program .…”

“…Moreover, explicit inclusion of a hydrogen bond energy term has traditionally been excluded from molecular force fields, based on the argument that it can be represented as a combination of the Van der Waals and electrostatic terms. However, results obtained from recent works have argued the importance of including a formal hydrogen bond energy term and provided the motivation for its calculation in our most recent version of SCOPE .…”

“…Here we utilize SCOPE to further establish the possibility of improving protein structure evaluations purely from energetics by use of artificial neural networks (ANN). The summary of our work reveals the importance of directly including a hydrogen bond energy term as well as the potential impact of utilizing the extended energy profile that is produced by SCOPE.…”