FOUR-BODY NON-ADDITIVITY AND THE TWIST OF B-DNA BASE-PAIR STEPS: A QUANTUM MONTE CARLO AND DENSITY FUNCTIONAL THEORY STUDY

Abstract

The lack of many-body non-additivity consideration in DNA bases is common in a lot of research, yet it contributes significantly to B-DNA molecule dynamism. Previous ab initio studies have shown substantial challenge to predict accurately the stacking interactions since they are inherent quantum mechanical phenomena that arise from the electron correlation effects in the DNA molecular system. However, recent studies have shown that the Quantum Monte Carlo (QMC) approaches can accurately describe stacking interaction through the inclusion of the correlation effects which are absent in methods such as Hartree-Fock and conventional functionals in Density Functional Theory (DFT). This study investigated four-body binding, four-body stacking and four-body twist of AA:TT using QMC method. In addition, the study of four-body term helical twist for AA’:TT’, A’T’:AT, T’A:TA’, GG’:CC’, G’C’:GC and C’G:CG was performed using DFT functionals namely, B3LYP, GGA and LDA. The QMC results provides for -12.80 kcalmol−1 AA:TT stacking which is agreeable with the CCSD(T) reference value of -13.10 kcalmol−1. The four-body term of -3.5 kcalmol−1 AA:TT predicts the importance of many-body inclusion in studying biomolecules. It was observed that the helical twist stacking energies were stronger for AA:TT and GG:CC geometrical arrangement and they would prefer a twist of approximately of 40◦, this is in agreement with the standard 35◦ to 45◦ degree range of the stable helical twist. Both four-body and helical twist influence stacking interaction energy to DNA sequence behavior. The findings of this study agree with previous works to within the allowed margins of chemical accuracy of 0.3 kcalmol−1 on the contribution of interstrand to staking stability, whereby their mutual compensation balance can control conformational variability. Keywords Stacking, Four-body Non-additivity, Twist.