Combining Experimental Data and Computational Methods for the Non-Computer Specialist

Abstract

Experimental methods are indispensable for the study of the function of biological macromolecules, not just as static structures, but as dynamic systems that change conformation, bind partners, perform reactions, and respond to different stimulus. However, providing a detailed structural interpretation of the results is often a very challenging task. While experimental and computational methods are often considered as two different and separate approaches, the power and utility of combining both is undeniable. The integration of the experimental data with computational techniques can assist and enrich the interpretation, providing new detailed molecular understanding of the systems. Here, we briefly describe the basic principles of how experimental data can be combined with computational methods to obtain insights into the molecular mechanism and expand the interpretation through the generation of detailed models.

Characterization of Phosphorylation-Dependent Antibody Binding to Cancer-Mutated Linkers of C2H2 Zinc Finger Proteins by Intact Transition Epitope Mapping-Thermodynamic Weak-Force Order Analysis

“…55 The integration of experimental data with computational approaches enables one to draw conclusions with atomic level resolution. 56 With the combination of mass spectrometry and molecular dynamics simulations, structural rearrangements of noncovalent protein complexes have been studied with respect to their transition from the condensed phase to the gas phase with single amino acid resolution. 39 Moreover, fine mapping of antibody−epitope interactions using molecular dynamics in conjunction with mass spectrometry, ITEM-TWO analysis, in particular, lead to the differentiation of orthodox binding and unorthodox binding, depending on small alterations of a recognition motif that were caused by single amino acid exchanges.…”

New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility

“…A combination of pure computational approaches with real data analysis to generate dynamic structural ensembles, best representing experimental outcomes, can be achieved in several ways. A recent review by Cardenas et al [177] provides concise guidance for non-computer specialists to maneuver through this complex endeavor. Briefly, three major strategies are presented-independent approach, guided simulation, and search and select (reweighting) approach.…”

The Influence of Pressure on Structural, Elastic, Piezoelectric and Dielectric Properties of R3c‐BiAlO3 Based on Ab Initio Calculations

“…Measurements of elastic properties under pressure, however, are usually very difficult and computational methods should compensate for the lack of experimental data. [36] Generally, isotropic moduli of elasticity are inaccessible by direct ab-initio calculations. The only way to evaluate these parameters is to calculate the Cijs monocrystalline elastic constants first and then transform these data into macroscopic quantities using mathematical mechanics-based methods.…”