Hot spot computational identification: Application to the complex formed between the hen egg white lysozyme (HEL) and the antibody HyHEL-10

摘要

The definition and comprehension of the hot spots in an interface is a subject of primary interest for a variety of fields, including structure-based drug design. Therefore, to achieve an alanine mutagenesis computational approach that is at the same time accurate and predictive, capable of reproducing the experimental mutagenesis values is a major challenge in the computational biochemistry field. Antibody/protein antigen complexes provide one of the greatest models to study protein-protein recognition process because they have three fundamentally features: specificity, high complementary association and a small epitope restricted to the diminutive complementary determining regions (CDR) region, while the remainder of the antibody is largely invariant. Thus, we apply a computational mutational methodological approach to the study of the antigen-antibody complex formed between the hen egg white lysozyme (HEL) and the antibody HyHEL-10. A critical evaluation that focuses essentially on the limitations and advantages between different computational methods for hot spot determination, as well as between experimental and computational methodological approaches, is presented. (c) 2006 Wiley Periodicals, Inc.