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α‐1 acid glycoprotein (AGP) is one of the most abundant plasma proteins. It fulfills two important functions: immunomodulation, and binding to various drugs and receptors. These different functions are closely associated and modulated via changes in glycosylation and cancer missense mutations. From a structural point of view, glycans alter the local biophysical properties of the protein leading to a diverse ligand‐binding spectrum. However, glycans can typically not be observed in the resolved X‐ray crystallography structure of AGP due to their high flexibility and microheterogeneity, so limiting our understanding of AGP's conformational dynamics 70 years after its discovery. We here investigate how mutations and glycosylation interfere with AGP's conformational dynamics changing its biophysical behavior, by using molecular dynamics (MD) simulations and sequence‐based dynamics predictions. The MD trajectories show that glycosylation decreases the local backbone flexibility of AGP and increases the flexibility of distant regions through allosteric effects. We observe that mutations near the glycosylation site affect glycan's conformational preferences. Thus, we conclude that mutations control glycan dynamics which modulates the protein's backbone flexibility directly affecting its accessibility. These findings may assist in the drug design targeting AGP's glycosylation and mutations in cancer. [ABSTRACT FROM AUTHOR]

The methanol-to-olefin process is a showcase example of complex zeolite-catalyzed chemistry. At real operating conditions, many factors affect the reactivity, such as framework flexibility, adsorption of various guest molecules, and competitive reaction pathways. In this study, the strength of first principle molecular dynamics techniques to capture this complexity is shown by means of two case studies. Firstly, the adsorption behavior of methanol and water in H-SAPO-34 at 350 °C is investigated. Hereby an important degree of framework flexibility and proton mobility was observed. Secondly, the methylation of benzene by methanol through a competitive direct and stepwise pathway in the AFI topology was studied. Both case studies clearly show that a first-principle molecular dynamics approach enables unprecedented insights into zeolite-catalyzed reactions at the nanometer scale to be obtained. [ABSTRACT FROM AUTHOR]

Dimension reduction is often necessary when attempting to reach longer length and time scales in molecular simulations. It is realized by constraining degrees of freedom or by coarse-graining the system. When evaluating the accuracy of a dimensional reduction, there is a practical challenge: the models yield vectors with different lengths, making a comparison by calculating their dot product impossible. This article investigates mapping procedures for normal mode analysis. We first review a horizontal mapping procedure for the reduced Hessian techniques, which projects out degrees of freedom. We then design a vertical mapping procedure for the 'implosion' of the all-atom (AA) Hessian to a coarse-grained scale that is based upon vibrational subsystem analysis. This latter method derives both effective force constants and an effective kinetic tensor. Next, a series of metrics is presented for comparison across different scales, where special attention is given to proper mass-weighting. The dimension-dependent metrics, which require prior mapping for proper evaluation, are frequencies, overlap of normal mode vectors, probability similarity, Hessian similarity, collectivity of modes, and thermal fluctuations. The dimension-independent metrics are shape derivatives, elastic modulus, vibrational free energy differences, heat capacity, and projection on a predefined basis set. The power of these metrics to distinguish between reasonable and unreasonable models is tested on a toy alpha helix system and a globular protein; both are represented at several scales: the AA scale, a Gō-like model, a canonical elastic network model, and a network model with intentionally unphysical force constants. Published 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The free energy surface of zeolite ‐ catalyzed reactions at real operating conditions is typically complex. As such, techniques that allow sampling of larger portions of the potential and free energy landscape are required to mimic experimental conditions as closely as possible. Various points on the free energy surface can be connected by a multitude of reaction paths. Mapping the free energy surface by advanced molecular dynamics simulations of a zeolite ‐ catalyzed reaction can hence be compared with studying a map in an atlas to discover the possible means of transport to travel between two cities. For the complete story see the Full Paper on page 9385 by B. Ensing, V. Van Speybroeck et al. [ABSTRACT FROM AUTHOR]