Preface

A physical and mathematical model is developed for the study of the vapor-diffusion process of protein crystal growth. This is a process widely used to grow high-quality crystals of proteins for the rapidly expanding fields of structural biology and drug design. In this process, an aqueous solution of protein is dynamically concentrated via a passive evaporation from a water drop to a reservoir. The kinetics of the process greatly influence the quality of the crystalline phase, albeit in an unknown manner and with the underlying physical aspects little understood. The model is solved analytically using the method of multiple timescales, identifying and exploiting the disparity in the timescales associated with the various transport mechanisms. Full nonlinear transient numerical simulations are also performed and compared with the analytical results and the data obtained from a benchmark experiment. The roles of the controlling parameters in the process are identified, and the requirements for experimental repeatability are explored, especially with regard to the temperature boundary conditions. Finally, it is proposed to use the verified analytical solution for process optimization to reduce the number of independent process variables under consideration.

Introduction

Structural biology is an emerging-late 20th century science, combining biology, biochemistry, computational science, applied mathematics, and other disciplines, to explicitly decipher the operational characteristics of biomolecules. Hereafter the term protein will be used to describe large conformationally flexible biomolecules that are made by the genetic sequence. Proteins are the building blocks of life, and are responsible for the thousands of individual biochemical actions in living things. Proteins are transcribed from the genetic material using amino acids that are combined via chemical bonds (peptide bonds) to form large molecules.