Article
Biochemistry & Molecular Biology
Rosario Tomarchio, Vincenzo Patamia, Chiara Zagni, Letizia Crocetti, Agostino Cilibrizzi, Giuseppe Floresta, Antonio Rescifina
Summary: Ordinary small molecule de novo drug design is time-consuming and expensive. Computational tools, such as molecular dynamics (MD) simulations and steered molecular dynamics (SMD), have shown promise in accelerating the drug design process. In this paper, we applied SMD to evaluate the binding properties of small molecules with FABP4, which is of interest for inhibiting FABP4 and has therapeutic potential in treating cancer and other diseases.
Article
Biochemistry & Molecular Biology
Ognjen Perisic, Willy Wriggers
Summary: The study utilized mutual information (MI) analysis to explore the mechanical resistance of the Top7 protein, providing a global overview of perturbation effects and proposing a novel mutation design based on residue hydropathy. The combination of MI analysis with conventional trajectory analysis offers valuable insights for engineering more resistant protein mutants without introducing covalent crosslinks, potentially preserving the protein's conformational space and unfolding pathway.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Polymer Science
Ran Chen, Chuanfu Luo
Summary: This study investigates the effect of stretching on the intrachain conformational ordering of PE, iPP, and iPB-1 single chains using all-atom steered molecular dynamics simulations. The results show that proper stretching can promote the formation of helical structures in iPP and iPB-1 chains. However, excessive force can lead to the instability and destruction of helices. The end-to-end distance of chains is suggested as a controlling factor for helix formation.
Article
Chemistry, Multidisciplinary
Lyman Monroe, Daisuke Kihara
Summary: The stability of protein structures can be measured by AFM pulling experiments, and this study used computational pulling to estimate the accuracy of protein structure models. It was found that near-native models can be selected by examining the break forces, indicating that high break force indicates high stability of models.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Rakesh Kumar Mishra, Sanchita Mukherjee, Dhananjay Bhattacharyya
Summary: Researchers attempted to understand the pathway of transforming double-stranded siRNA into single-stranded RNA using steered molecular dynamics simulations. They found different forces and energies were required during this process, and believe that utilizing this mechanistic knowledge may enhance the success rate of siRNA sequence design for gene silencing.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Ali A. Rabaan, Bashayer M. AlShehail, Muhammad A. Halwani, Amer Alshengeti, Mustafa A. Najim, Mohammed Garout, Huda A. Bajunaid, Saleh A. Alshamrani, Mona A. Al Fares, Mohammed Alissa, Ameen S. S. Alwashmi
Summary: Zika virus (ZIKV) poses a major public health threat and there is an urgent need for a highly effective medicinal molecule to control the infection. This study used computational methods to identify a potent natural compound that can inhibit the ZIKV NS5 methyltransferase. Screening and analysis revealed three compounds, Adenosine 5'-monophosphate monohydrate, Tubercidin, and 5-Iodotubercidin, which showed stable binding, strong interactions, and higher total binding free energy compared to the reference compound, SAH. These compounds have potential for drug development against Zika virus infections.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Rakesh Kumar Mishra, Lakshmi Maganti
Summary: The stability of the DNA double helix is significantly increased in the presence of covalently bonded drugs, which can potentially help in designing pharmaceutical drugs to target cancer cells. The study shows that disruption of hydrogen bonds and variation of stacking overlap parameters provide evidence of symmetry during rupture and asymmetry in the unzip event, indicating a promising pathway to open the double helix at a specific position.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Caley Allen, Hailey R. Bureau, T. Dwight McGee, Stephen Quirk, Rigoberto Hernandez
Summary: The study used the ASMD method to investigate two different helical peptides and found that the choice of force field greatly affects the results, with the c36 force field version performing the best in forced unfolding simulations.
Article
Chemistry, Physical
Yi Zhuang, Hailey R. Bureau, Stephen Quirk, Rigoberto Hernandez
Summary: ASMD is a variant of SMD that reduces the number of trajectories needed by discarding those that deviate far from the equilibrium path in stages. FR-ASMD is preferred for small systems with a single unfolding pathway, while MB-ASMD is preferred for complex energy landscapes of multi-domain proteins.
MOLECULAR SIMULATION
(2021)
Article
Computer Science, Interdisciplinary Applications
Keshab B. Thapa, Kalpana S. Katti, Dinesh R. Katti
Summary: This study evaluated the mechanical response of sodium montmorillonite (NaMt) intercalated with fluids of different polarities. The results showed that the polarity of the fluids and the fluid content in the clay interlayer space played a vital role in the clay's shear strength parameters and nonbonded interactions energies. The shear stress versus shear strain response of the expansive clay depended on the normal stress and fluid polarity.
COMPUTERS AND GEOTECHNICS
(2023)
Review
Chemistry, Multidisciplinary
Peter R. Spackman, Arnaud Grosjean, Sajesh P. Thomas, Durga Prasad Karothu, Pance Naumov, Mark A. Spackman
Summary: This review provides a critical and comprehensive overview of experimental measurements of complete elastic constant tensors for molecular crystals, comparing them with calculations from different methods. The comparisons identify outliers and aim to stimulate further research correlating mechanical properties with crystal structure.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Shitao Zhang, Yi Wang, Lu Han, Xueqi Fu, Song Wang, Wannan Li, Weiwei Han
Summary: Multiple drugs are available for the treatment of type 2 diabetes, with alpha-glucosidase inhibitors playing a key role in controlling postprandial glucose levels. Molecular dynamics simulations show that DSK may affect the flexibility of certain domains in NtMGAM, potentially influencing the binding progress. ASMD simulations indicate that DSK can escape from NtMGAM more easily than acarbose due to interactions with specific residues. These findings may provide valuable insights for designing new alpha-glucosidase inhibitors for type 2 diabetes treatment.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Physical
Honghua Zhao, Hanwen Cui, Shuqi Jiang, Waleed Awadalseed, Jing Guo, Wei Yang, Xin Kang
Summary: Molecular dynamics (MD) method was used to simulate the nano mechanical behavior of Na-, K-, and Ca-montmorillonite (MMT) under uniaxial tension and compression, and effects of loading direction and temperature were explored. Significant differences were observed in the nano mechanical behavior of montmorillonite in different directions, with in-plane tensile and compressive properties being stronger than those perpendicular to the crystal plane. The nano mechanical properties of Na-MMT showed a negative relation with temperature and decreased with increasing hydration. The stiffness coefficients were influenced by hydration and interlayer cations. The tensile strength of Ca-MMT was the smallest among the three types of montmorillonite. The bulk modulus, shear modulus, and Young's modulus of polycrystal Na-, K-, and Ca-MMT decreased with increasing hydration, while Poisson's ratio remained unchanged. Tension failure was caused by slip plane and bond breaks, while compression failure was caused by local buckling and shear band formation.
Article
Chemistry, Medicinal
Natasha Gupta Vergara, Megan Gatchel, Cameron F. Abrams
Summary: Recent experimental work has shown that the N501Y mutation in the SARS-CoV-2 S glycoprotein's receptor binding domain increases binding affinity to ACE2 by reducing the entropic penalty for complex formation. This study uses molecular dynamics simulations and free-energy calculations to assess the impact of the N501Y mutation on the enthalpy and entropy of binding. The results suggest that the mutation leads to a less favorable enthalpy of binding, but this is compensated for by an entropically favorable increase in quaternary flexibility and residue fluctuations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Elton Jose Ferreira Chaves, Luiz Eduardo Gomes da Cruz, Itacio Queiroz Mello Padilha, Carlos Henrique Silveira, Demetrius Antonio Machado Araujo, Gerd Bruno Rocha
Summary: This study conducted computational research to explore small molecules that can inhibit the ricin toxin, identifying potential inhibitors through a virtual screening protocol from a database. The structure-based virtual screening and novel scoring method were effective in finding compounds that strongly bind to the RTA active site, with SCF00-451 identified as a promising candidate to inhibit the plant toxin's killing activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
