CPM Seminar

Molecular Recognition in Biological Systems.
What can simulations tell us?

Giorgio Colombo

CNR Istituto di Chimica del Riconoscimento Molecolare
Milan

Molecular recognition and spontaneous self-assembly are at the basis of the organization of all biomolecular systems. In the case of proteins and peptides, the information needed to control these processes is encoded in the sequence. This determines the form, symmetry and structural features of the interacting partners that in the end regulate the properties of biochemical pathways. Understanding the correlations between sequence structure and dynamics in proteins and peptides at an atomistic level of resolution still represents one of the grand challenges of modern biological chemistry. In this context, computer simulations represent a valuable approach to understand recognition and spontaneous self-organization (folding, aggregation and assembly of complexes), processes that cannot be directly observed experimentally.

Herein, examples illustrating the extent to which simulations can be used to understand these phenomena will be presented. I will cover 1) the problem of peptide-receptor recognition and the use of the information obtained for the design of new drug-like molecules and 2) the study of the effects of different single point mutations on the self-organization properties of designed amyloidogenic peptide sequences.

Simulation results are compared with experimental observations. The simulations have provided evidence for the influence of a small number of sequence-specific interactions with well defined stereochemical constraints on all the aspects of organization in protein systems. Our results suggest that simulations can be applied to detect the critical physico-chemical determinants of a certain process and be of help to the design of new experiments.