Restrictions of sequence on the thickness of globular protein molecules

Abstract

A model for globular protein molecules based on a linear and random sequence of polar and nonpolar amino acids was developed. Polar amino acids were assumed to be always in contact with the aqueous solvent, while nonpolar amino acids were assumed to have a tendency to be buried. Considerations of amino-acid dimensions indicated that only runs of four or more nonpolar amino acids in a row could allow some amino acids to be more than 1-nm (10-A) removed from the surface of the protein. The expected volume fraction of a protein molecule that could be more than 1-nm removed from the surface was obtained with the assumption of a random sequence. Calculation of this volume fraction for a number of simple geometric shapes indicated that some nonpolar amino acids must be exposed to solvent and that the maximum average thickness of globular proteins should be 3-4 nm. Good agreement with published protein dimensions was obtained.