Role of medium- and long-range interactions in discriminating globular andmembrane proteins

The analysis of inter-residue interactions in protein structures provides c onsiderable insight to understand their folding and stability. We have prev iously analyzed the role of medium- and long-range interactions in the fold ing of globular proteins. In this work, we study the distinct role of such interactions in the three-dimensional structures of membrane proteins. We o bserved a higher number of long-range contacts in the termini of transmembr ane helical (TMH) segments, implying their role in the stabilization of hel ix-helix interactions. The transmembrane strand (TMS) proteins are having a ppreciably higher long-range contacts than that in all-beta class of globul ar proteins, indicating closer packing of the strands in TMS proteins. The residues in membrane spanning segments of TMH proteins have 1.3 times highe r medium-range contacts than long-range contacts whereas that of TMS protei ns have 14 times higher long-range contacts than medium-range contacts. Res idue-wise analysis indicates that in TMH proteins, the residues Cys, Glu, G ly, Pro, Gin, Ser and Tyr have higher long-range contacts than medium-range contacts in contrast with all-alpha class of globular proteins. The charge d residue pairs have higher medium-range contacts in all-alpha proteins, wh ereas hydrophobic residue pairs are dominant in TMH proteins. The informati on on the preference of residue pairs to form medium-range contacts has bee n successfully used to discriminate the TMH proteins from all-alpha protein s. The statistical significance of the results: obtained from the present s tudy has been verified using randomized structures of TMH and TMS protein t emplates. (C) 2001 Elsevier Science B.V. All rights reserved.