Nuclear dynamics investigation of the initial electron transfer in the cyclobutane pyrimidine dimer lesion repair process by photolyases

TL;DR

This study models the initial electron transfer in DNA repair by photolyases, revealing how specific nuclear motions influence the rate and coherence of the process, using a quantum dynamical approach based on experimental data.

Contribution

It introduces a non-empirical quantum dynamical model of electron transfer in photolyases, highlighting the impact of nuclear degrees of freedom on reaction dynamics.

Findings

Low frequency flavin bending mode slows electron transfer.

Nuclear motions induce decoherence affecting ET efficiency.

Model aligns with experimental transient spectroscopy data.

Abstract

Photolyases are proteins capable of harvesting the sunlight to repair DNA damages caused by UV light. In this work we focus on the first step in the repair process of the cyclobutane pyrimidine dimer photoproduct (CPD) lesion, which is an electron transfer (ET) from a flavine cofactor to CPD, and study the role of various nuclear degrees of freedom (DOF) in this step. The ET step has been experimentally studied using transient spectroscopy and the corresponding data provide excellent basis for testing the quality of quantum dynamical models. Based on previous theoretical studies of electronic structure and conformations of the protein active site, we present a procedure to build a diabatic Hamiltonian for simulating the ET reaction in a molecular complex mimicking the enzyme's active site. We generate a reduced nuclear dimensional model that provides a first non-empirical quantum dynamical description of the structural features influencing the ET rate. By varying the nuclear DOF parametrization in the model to assess the role of different nuclear motions, we demonstrate that the low frequency flavin butterfly bending mode slows ET by reducing Franck-Condon overlaps between donor and acceptor states and also induces decoherence.