Evaluation performance of substitution matrices, based on contacts between residue terminal groups

Abstract

Sequence alignment is a standard method for the estimation of the evolutionary, structural, and functional relationships among amino acid sequences. The quality of alignments depends on the used similarity matrix. Statistical contact potentials (CPs) contain information on contact propensities among residues in native protein structures. Substitution matrices (SMs) based on CPs are applicable for the comparison of distantly related sequences. Here, contact between amino acids was estimated on the basis of the evaluation of the distances between side-chain terminal groups (SCTGs), which are defined as the group of the side-chain heavy atoms with fixed distances between them. In this paper, two new types of CPs and similarity matrices have been constructed: one based on fixed cutoff distance obtained from geometric characteristics of the SCTGs (TGC1), while the other is distance-dependent potential (TGC2). These matrices are compared with other popular SMs. The performance of the matrices was evaluated by comparing sequence with structural alignments. The obtained results show that TGC2 has the best performance among contact-based matrices, but on the whole, contact-based matrices have slightly lower performance than other SMs except fold-level similarity.

CONTSOR—A new knowledge‐based fold recognition potential, based on side chain orientation and contacts between residue terminal groups

“…The structural characteristics used in fold recognition can be divided into three groups in accordance with the forces they reflect: the first group includes characteristics connected with the given conformations or the type of the secondary structure of the residue,6, 16, 21 mainly reflecting the results of short‐ and medium‐range interactions (i.e., intraresidue interactions or interactions between residues located close to each other in the sequence); the second group includes the characteristics connected with the entropy (these are for example: the solvent accessible surface areas, distance residue from the center of globule6, 13, 16, 22 reflecting the results of hydrophobic effect); the third group includes characteristics connected with the tight close‐packing of side chains. This is for example, diverse variants of close contacts between residues23–25 mainly reflecting the results of interactions between residues far apart in the sequence (long‐range).…”

“…In our previous works threading potential SORDIS incorporated the side chain orientation angle in relation to hydrophobic core centers, the distance of the residues from the geometrical centers of the protein globule and secondary structure terms26, 27 was described. The potential based on close contacts between amino acid side chain terminal groups has also been developed 25, 28…”

“…In this paper we present a new combined fold recognition potential CONTSOR based on structural characteristics that incorporates SORDIS27 and the contact‐based potential 25. This potential takes into account all three groups of structural characteristics.…”