Dynamic multiple-scattering treatment of X-ray absorption: Parameterization of a new molecular dynamics force field for myoglobin

Abstract

We present a detailed analysis of the X-ray absorption near-edge structure (XANES) data on the Fe K-edge of CO Myoglobin based on a combined procedure of Molecular Dynamics (MD) calculations and MXAN (Minuit XANes) data analysis that we call D-MXAN. The ability of performing quantitative XANES data analysis allows us to refine classical force field MD parameters, thus obtaining a reliable tool for the atomic investigation of this important model system for biological macromolecules. The iterative procedure here applied corrects the greatest part of the structural discrepancy between classical MD sampling and experimental determinations. Our procedure, moreover, is able to discriminate between different heme conformational basins visited during the MD simulation, thus demonstrating the necessity of a sampling on the order of tens of nanoseconds, even for an application such X-ray absorption spectroscopy data analysis.

Ligand pathways in neuroglobin revealed by low-temperature photodissociation and docking experiments

“…Systematic errors are mostly owing to the poor approximation used for the phenomenological broadening function À(E) adopted in the MXAN method , which mimics the electronic damping. However, systematic errors do not appreciably affect structural results, as has already been demonstrated for model systems such as Fe-porphyrin, Fe-heme and Fe(CN) 6 , confirming that XANES is more dependent on the geometry of the atomic cluster rather than its electronic structure (Arcovito et al, 2005;D'Angelo et al, 2008D'Angelo et al, , 2010Della Longa et al, 2001Hayakawa et al, 2004;Lima et al, 2014;Chillemi et al, 2018). Notably, in our XANES analysis, the largest observed r.m.s.d.…”

Understanding the Role of R266K Mutation in Cystathionine β-Synthase (CBS) Enzyme: An in Silico Study

“…Molecular dynamics simulations for various Heme containing proteins are occasionally reported in the literature using different force field models. [25][26][27][28][29][30] However to the best of our knowledge, the forcefields for hexa-coordinated Heme with cystine and histidine bound at the axials positions were never developed. In the hCBS, Doss and co-workers applying In Silico tools and MD simulations investigated the structure-functional insight into the effect of SNP on the stability and activity of mutant CBS.…”

“…A diverse functionality of the heme moiety in conjunction with different proteins have been explored using classical molecular dynamics simulation under different force field models. [25][26][27][28][29] The unavailability of Amber force field parameters for cystine and histidine bound hexacoordinated heme present in hCBS calls for its parameterization under this specific chemical environment. substitution in the catalytic function and protein conformation.…”

Recent developments of X‐ray absorption spectroscopy as analytical tool for biological and biomedical applications

“…In addition, the support of theoretical calculations, whether XAS spectra or the use of classical molecular mechanics/dynamics (MM/MD) is mandatory in many cases to verify the accuracy of structure data obtained by experimental methods. [11][12][13][14] For significantly improved signal-to-noise ratio for studying biological systems, methods providing high energy resolution fluorescence detected XAS (HERFD-XAS) are constantly gaining importance. [15][16][17][18] In cases where the analyte concentration is extremely low, in nanogram or even picogram range, the use of total reflection X-ray fluorescence XAS (TXRF-XAS) is the variant of choice.…”