Amino Acid Correlation Functions in Protein Structures.

Klemen Kržišnik,Tomaz Urbic

doi:10.17344/acsi.2015.1538

Abstract

Understanding the spatial folding of proteins from their amino acid sequences has an enormous potential in contemporary life sciences. The ability to predict secondary and tertiary structures from primary ones through the use of computers will enable a much faster and more efficient discovery of organic substances with therapeutic or otherwise bioactive potential, largely eliminating the need for synthesis and testing of large numbers of organic substances for physiological effects. Our manuscript presents an application of correlation function analysis, usually used to describe properties of liquids, to protein structures in order to elucidate statistically favored distances among amino acids. Pairwise distribution functions were calculated between C-alpha atoms of 20 amino acids in a large ensemble of Protein Data Bank structures. The correlation functions show characteristic distances in amino acid interactions. Different propensities for forming various secondary structure elements among all 210 possible amino acid pairs have been visualized and some have been interpreted. Notably, we found helices to be surprisingly common among certain pairs.

Highlights

Proteins are the basic building blocks of life
Pairwise distribution functions have proven themselves to be a useful tool in the theory of liquids and we show they can be of help in elucidating amino acid interactions
Pairwise distribution functions were calculated between C-alpha atoms of 20 amino acids in a large ensemble of Protein Data Bank structures

Summary

Introduction

Proteins are the basic building blocks of life They are polymers made of 20 proteinogenic amino acids, some of which can be further modified post synthesis. The main problem of protein folding is the determination of a protein’s native structure based on its amino acid sequence.[1] In cellular and other physiological solutions proteins assume a well-defined three dimensional structure, presumed to be of the lowest free energy state.[2] The structure is described on four levels. Starting from a linear sequence of amino acids (primary structure), a relatively small protein is believed to adopt its native conformation (of minimum free energy) through the interplay of intermolecular forces and thermal energy kBT (kB being Boltzmann’s constant and T being absolute temperature).[1] The problem of protein folding has been studied with rather different approaches. On one hand, Ising-like models allow us to enumerate exhaustively all confor-

Methods

Results

Conclusion