Theoretical Aspects of Molecular Recognition

Molecular recognition is a key process in non-covalent interactions, which determines, among others, host-guest complexation, drug action and protein-protein interaction. A simple and attractive formulation is the lock-and-key analogy defining the host as a lock accommodating the guest as a key. We stress three major aspects of molecular recognition, determining both complementarity between host and guest and similarity within a group of guest molecules. These aspects are: steric, i.e. maximization of close contacts, electrostatic, i.e. maximization of electrostatic attraction between host and guest, as well as hydrophobic, i.e. avoiding hydrophobic hydration, which can be reached by the maximization of apolar contacts between interacting molecules. Some examples are presented from our laboratory: the complexes of acylaminoacyl peptidase with small peptides, the effect of heparin binding on inhibitory potency of C1- inhibitor as well as small-molecule ligand binding to prolyl oligopeptidase and calmodulin

Aspects of Molecular Beauty

Molecules are objects of nature like a landscape, a plant, an animal or a human. Accordingly they may be beautiful, especially in the eyes of a chemist who works at his/her computer and constructs, inspects and understands molecular models. These models serve chemical thinking, experiments can be designed with much more certainty, molecular processes can be understood in more detail if we “see” our objects, i.e. we use more or less appropriate models reflecting the properties and action of the molecules. In this paper I discuss some aspects of molecular beauty and I must admit that my discussion is strongly biased. The reader will understand that I do like molecules, I enjoy work with them on the screen and presenting them in my lectures to laymen or to experts. I would share this feeling with artists and aesthetes, strongly believing that they may share my feelings upon inspection of colorful and rich in shape molecular models

Calmodulin in Complex with Proteins and Small Molecule Ligands: Operating with the Element of Surprise. Implications for Structure-Based Drug Design

Calmodulin plays a role in several life processes, its flexibility allows binding of a number of different ligands from small molecules to amphiphilic peptide helices and proteins. Through the diversity of its functions, it is quite difficult to find new drugs, which bind to calmodulin as a target. We present available structural information on the protein, obtained by X-ray diffraction, nuclear magnetic resonance spectroscopy and molecular modeling and try to derive some conclusions on structureactivity relationships