Decomposing protein–DNA binding and recognition using simplified protein models

We analyze the role of different physicochemical factors in protein/DNA binding and recognition by comparing the results from all-atom molecular dynamics simulations with simulations using simplified protein models. These models enable us to separate the role of specific amino acid side chains, formal amino acid charges and hydrogen bonding from the effects of the low-dielectric volume occupied by the protein. Comparisons are made on the basis of the conformation of DNA after protein binding, the ionic distribution around the complex and the sequence specificity. The results for four transcription factors, binding in either the minor or major grooves of DNA, show that the protein volume and formal charges, with one exception, play a predominant role in binding. Adding hydrogen bonding and a very small number of key amino acid side chains at the all-atom level yields results in DNA conformations and sequence recognition close to those seen in the reference all-atom simulations.