Preface

The biological functionality of a soluble protein can only be fully grasped when its aqueous interface becomes an integral part of the structural analysis. Furthermore, the acknowledgment of how exquisitely the structure and dynamics of proteins and their aqueous environment are related attests to the overdue recognition that biomolecular phenomena cannot be grasped without dealing with interfacial behavior at multiple scales. This is essentially the dictum that guided the writing of this book. The book focuses primarily on the biological and pharmacological role of interfacial forces determined by the embedding of protein structure in a physiological aqueous environment. By providing a suitable statistical mechanical apparatus to handle epistructural (“around the structure”) interfacial phenomenology, the book becomes uniquely positioned to address core problems in molecular biophysics. It highlights the importance of interrelated concepts like water hydrogen-bond frustration, interfacial tension and non-Debye dielectrics in delineating a solution to the protein folding problem, in unraveling the physicochemical basis of enzyme catalysis and protein associations, in delineating the molecular etiology of aberrant protein aggregation, and in rationally designing molecular-targeted therapies. The book incrementally builds upon a statistical mechanical apparatus to deal with epistructural interfaces in a biological context. As it extends previous work in interfacial physics to the biological context, the book strives to maintain the level of rigor expected from a researcher devoted to interfacial physics, notwithstanding the daunting complexities of biomolecular systems. In the biological/biomedical context, the book introduces the necessary controls and experimental corroborations to validate the physical treatment. Furthermore, molecular dynamics and quantum