Hybrid QM/MM study of a fundamental biological interaction surrounded by its protein environment

• Type: Article in International Scientific Journal
• Date: 2000

Authors

Magalhaes, AL (Author) FCUP; Maigret, B (Author) Other; Gomes, JANF (Author) FCUP; Ramos, MJ (Author) FCUP

Journal

Title: INTERNET JOURNAL OF CHEMISTRY

Vol. 3

Pages: art. no.-11

ISSN: 1099-8292

Publisher: INFO TRUST LTD

Indexing

ISI Web of Knowledge - 1 Citation

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-001-038

Abstract (EN): The three-dimensional structures of the antigen/antibody complexes of hen egg white lysozyme with Fab HyHEL-5 and Fab D44.1 show a hydrophobic hole in their interface region, in which an interaction between the side-chains of two arginine residues from the lysozyme and two glutamic acids from the heavy chain of the Fab fragments is observed. In this work, the four interacting residues were treated using a quantum mechanical method, and the rest of the whole protein was handled with a molecular mechanics force field. Slight different conformations are adopted by the interacting system in the interface region of both complexes. In addition, HyHEL-5 Fab/Lysozyme complex shows a preference to the formation of salt bridges between the glutamates and the arginines, whereas an interaction between neutral side-chains is energetically favorable in the D44.1 Fab/Lysozyme complex. The difference in enthalpic contributions obtained with these two distinct protonation states can be responsible for the 1000-fold increase in the association constant of the HyHEL5 Fab/Lysozyme complex, when compared with the D44.1. Fab/Lysozyme.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13