Assessment of Reliability of Conformational Energy Computation Program of Proteins

1986 Fiscal Year Final Research Report Summary

• Project/Area Number: 60580223
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: 生物物性学
• Research Institution: Aichi Medical University (1986); Kyoto Prefectural University of Medicine (1985)
• Principal Investigator: ISOGAI Yoshinori Associate Professor Aichi Medical University, 医学部, 助教授 (60079697)
• Project Period (FY): 1985 – 1986
• Keywords: Protein / Conformational Analysis / Energy Computation / Tertiary Structure

Research Abstract

Reliability of a computer program for the calculation of conformational energy of protein molecules is assessed by examining whether the progaram is able to distinguish the amino acid sequence modifications(shuffling the sequence preserving the amino acid composition unchanged) imposed on natural sequence of a protein.
ECEPP(Empirical Conformation Energy Program for Peptides) and BPTI were adopted as the objective program and protein for the assessment, respectively. First, the refinement of BPTI crystal coordinates of atoms was carried out under the condition of fixed bond lengths, bond angles and planarity of the peptide bonds. Minimization of the conformational energy of BPTI starting from the refined structure was carried out, and a conformation with -37.1kcal/mol ECEPP energy was found to be the minimum energy conformation. Second, several sequences in which about 20-40% residues of BPTI were shuffled mechanically preserving the amino acid composition unchanged were generated and put under the search of the minimum energy conformation. These search were unsuccessful to reach minimum energies, because there remained overlaps between side chain atoms notwithstanding vigorous efforts, and simply left a lesson that shuffling should be carried out not mechanically but systematically. Third, the minimum energy conformation of a sequence in which Thr-32 and Val-34 were exchanged was searched, and one with -26.3kcal/mol which was higher by about 10kcal/mol than that of natural sequence was found. This result suggests that ECEPP can reflect the specificity of amino acid sequences.
Since the number of samples examined here is no more than one at present, it is quite difficult to draw a definite conclusion in some shape or other. It is expected that the number of samples is increased enough to assess the reliability of ECEPP program by exchanging the amino acid sequence systematically starting from the sequence examined above.