Quantifying Steric and Hydrophobic Influence of Non-Standard Amino Acids in Proteins That Undergo Post-Translational Modifications

Luiz F O Rocha

doi:10.11648/j.bmb.20170202.11

Abstract

Non-standard amino acids in protein post-translational modifications aid in a wide variety of biological functions and processes, furnishing expansion from the genome to the proteome. First, from structural examinations in unmodified proteins with only standard amino acids, this work empirically obtains numeric relations that reveal how instruction transfers occur between native-state structures. Next, from these relations, the influence of non-standard amino acids inside post-translationally modified proteins is quantified by successfully predicting the contents of large and hydrophobic residues in helices and β-strands for 210 inspections performed. This suggests a twofold molecular mechanism by the fundamental biophysicochemical properties (residue volume and hydrophobicity), and concludes that the utilized non-standard amino acids have limited global influence at the residue level. Our prediction method provides a better underlying understanding of molecular interactions and mechanisms, and is particularly promising in terms of surveying further modified proteins.

Highlights

After biosynthesis from genetic instructions, many peptide and protein species undergo post-translational modifications on the endoplasmic reticulum in order to exert their specialized biological purposes, control varied cellular processes, modulate chemical reactions, and interact with other molecules
Taking the above restrictive conditions, and among several sequence extensions that were extensively investigated, we opt for a systematic analysis of 35-residue modified and unmodified proteins deposited in the Protein Data Base (PDB) [21]
The 35-residue unmodified proteins consist of 39 exemplars, while the modified ones include 16 exemplars and residue sequences with at least one of the nine non-standard chemical compounds (ABA, ACE, DNP, DPR, IIL, NH2, NLE, pyroglutamic acid (PCA), and SIN), whose skillful roles [6,7,8,9,10,11,12,13,14,15,16,17,18,19] were previously described in the Section 1

Summary

Introduction

After biosynthesis from genetic instructions, many peptide and protein species undergo post-translational modifications on the endoplasmic reticulum in order to exert their specialized biological purposes, control varied cellular processes, modulate chemical reactions, and interact with other molecules. These modifications may aid to alter chemical properties, folding events, macromolecular stabilities, activity states, and subcellular locations [1,2] of peptides and proteins. There are several posttranslational modifications, including those made through additions of non-standard amino acids to one or more standard amino acid residues to redirect the protein chain in the proper direction and, influencing or assisting its charge, hydrophobicity, conformation, stability and function [4]. The post-translational succinylation (or insertion of a group succinyl (SIN) to ends of a chain) in the fragmentation of biopolymers can both solubilize the peptide derivatives and block the action of enzymes [10], as well as inhibiting hydrolysis [11]

Methods

Results

Conclusion