Article
Biochemistry & Molecular Biology
Monica L. Fernandez-Quintero, Eugene F. DeRose, Scott A. Gabel, Geoffrey A. Mueller, Klaus R. Liedl
Summary: In this study, the conformational diversity of an anti-GFP-binding nanobody was characterized using molecular dynamics simulations and experimental data from NMR spectroscopy. The results showed excellent agreement between the distance maps obtained from NMR and MD simulations, as well as similar conformational spaces for simulations with and without time-averaged restraints. The motions observed in the ps-ns timescale, particularly in the CDR3 loop, also showed good agreement between measured and calculated order parameters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Monique J. Rogals, Alexander Eletsky, Chin Huang, Laura C. Morris, Kelley W. Moremen, James H. Prestegard
Summary: Glycans attached to glycoproteins play important roles in stability, protein-protein interactions, and signal transduction. This study focuses on the conformation of glycans and uses NMR resonances to identify preferred glycan conformers. The results show that the preferred conformers have extensive contacts with the protein surface, which are influenced by interactions between specific glycans and hydrophobic pockets on the protein surface.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Monique J. Rogals, Alexander Eletsky, Chin Huang, Laura C. Morris, Kelley W. Moremen, James H. Prestegard
Summary: Glycans attached to glycoproteins play important roles in stability, protein-protein interactions, and signal transduction. The conformation of these glycans is critical and highly variable, often sampling a multitude of conformations. In this study, long-range pseudo-contact shifts of NMR resonances were used to identify preferred conformations of glycans attached to a model glycoprotein. The analysis revealed that the preferred glycan conformers have extensive contacts with the protein surface, potentially due to interactions between N-acetyl methyls of GlcNAc residues and hydrophobic surface pockets.
ACS CHEMICAL BIOLOGY
(2022)
Article
Immunology
Monica L. Fernandez-Quintero, Katharina B. Kroell, Florian Hofer, Jakob R. Riccabona, Klaus R. Liedl
Summary: This study characterizes the role of residue 71(H) in antibody design, showing its influence on CDR-H2 loop conformation and the diversity and population shifts of CDR-H1 and CDR-H3 loops. The study demonstrates that all CDR loop movements are correlated, leading to conformational rearrangements and changes in interface angle distributions, ultimately affecting different paratope states in solution.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Physical
Sergio Perez-Conesa, Eric G. Keeler, Dongyu Zhang, Lucie Delemotte, Ann E. McDermott
Summary: The pH-gated prokaryotic channel KcsA has been extensively studied as the first potassium channel with an x-ray structure determined, but questions related to the allosteric coupling between its gates remain open. Solid-state nuclear magnetic resonance (SSNMR) can provide insights into the molecular basis of activation mechanisms by studying the wild-type protein under activating conditions, and simulation techniques such as molecular dynamics (MD) simulations can help determine the activated state captured in SSNMR experiments.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Immunology
Emily R. Rhodes, Jonathan G. Faris, Brian M. Petersen, Kayla G. Sprenger
Summary: Through molecular dynamics simulations, this study found that framework mutations can significantly alter the distribution of VH-VL interface angles, which in turn affect the local flexibility of antibodies by changing the solvent accessible surface area. These findings emphasize the limitations of static antibody crystal structures and demonstrate the dynamic nature of antibodies in solution. The study further highlights the importance of framework mutations in antibody structure and lays the foundation for establishing design principles to create antibodies with increased specificity, stability, and breadth.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Engineering, Mechanical
Baozhen Li, Jianyong Li, Jinhuan Xu, Tong Xuan, Wengang Fan
Summary: This paper investigates the effect of cracking on the deformation behavior of GaAs with varied crystal orientations during processing. Molecular dynamics simulations were conducted to scratch GaAs using a diamond indenter with a single asperity in different crystal orientations. The findings provide direct evidence that cracking alters the deformation behavior of GaAs at the atomic level, which is attributed to the distribution of tensile stresses and the fracture surface. This work contributes to a better understanding of the deformation mechanism anisotropy of GaAs in different crystal orientations.
TRIBOLOGY INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
N. Gao, Z. W. Yao, G. H. Lu, H. Q. Deng, F. Gao
Summary: The study found a new diffusion mechanism for <100> interstitial dislocation loops in BCC iron using self-adaptive accelerated molecular dynamics, which represents a significant step towards understanding the mechanical behavior and microstructure evolution of the material.
NATURE COMMUNICATIONS
(2021)
Article
Food Science & Technology
Ting Nie, Fanqiang Meng, Fengxia Lu, Jing Sun, Xiaomei Bie, Zhaoxin Lu, Yingjian Lu
Summary: Salmcide-p1 is an enzybiotic derived from Salmonella bacteriophage fmb-p1 with broad-spectrum antibacterial activity against Gram-negative bacteria. This study revealed the mechanism of interaction between Salmcide-p1 and bacterial peptidoglycan, showing that catalytic lysis of peptidoglycan is a key mechanism for its inhibitory effect.
Article
Chemistry, Physical
D. Aristoff, J. Copperman, G. Simpson, R. J. Webber, D. M. Zuckerman
Summary: The weighted ensemble (WE) method, an enhanced sampling approach, has gained popularity in computational biochemistry due to improved hardware, software, and algorithmic advancements. Recent results have led to greater computational efficiency, particularly through variance reduction approaches for managing trajectories in systems of any dimensionality.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Biancamaria Farina, Corvino Andrea, Annarita Del Gatto, Daniela Comegna, Sonia Di Gaetano, Domenica Capasso, Antonella Paladino, Clementina Acconcia, Maria Teresa Gentile, Michele Saviano, Roberto Fattorusso, Laura Zaccaro, Luigi Russo
Summary: The study developed an on-cell NMR-based method to investigate molecular determinants driving receptor-ligand interactions on living cells surface. By combining high-resolution structural and dynamics NMR data with Molecular Dynamics simulations and Molecular Docking studies, the approach is able to effectively explore the mechanism under native conditions.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Applied
Rungroj Chanajaree, Wutthigrai Sailuam, Kompichit Seehamart
Summary: This study investigated the loading dependence of self-diffusion coefficient, diffusion selectivity, and structural properties of pure CH4, H2S, and their mixtures in MIL-47(V) material using MD simulations. The preferential adsorption sites and molecular structures of gas molecules in the lattice were determined, and the diffusion behavior of gas molecules in the lattice was further studied. The findings were examined and compared to previous research.
MICROPOROUS AND MESOPOROUS MATERIALS
(2022)
Article
Chemistry, Physical
Zhi-Chao Ma, Xiao-Zhi Tang, Yong Mao, Ya-Fang Guo
Summary: The deformation mechanisms of Mg, Zr, and Ti single crystals with different orientations have been studied using molecular dynamics simulations, revealing that twinning plays a crucial role in plastic deformation, especially in Ti where multiple deformation mechanisms are activated. The results show that the activation of basal, prismatic, and pyramidal dislocations are influenced by factors like the Schmid factor and critical resolved shear stresses (CRSS), which vary among the different materials studied.
Article
Multidisciplinary Sciences
Yusuke Kawashima, Tomoyuki Hamachi, Akio Yamauchi, Koki Nishimura, Yuma Nakashima, Saiya Fujiwara, Nobuo Kimizuka, Tomohiro Ryu, Tetsu Tamura, Masaki Saigo, Ken Onda, Shunsuke Sato, Yasuhiro Kobori, Kenichiro Tateishi, Tomohiro Uesaka, Go Watanabe, Kiyoshi Miyata, Nobuhiro Yanai
Summary: Singlet fission (SF) can create spin-polarized quintet states in organic systems, and here the authors demonstrate that SF in supramolecular assemblies of pentacene chromophores improves the sensitivity of magnetic resonance of water molecules through dynamic nuclear polarization in a water-glycerol glass.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Sangmin Lee, Thi Vo, Sharon C. Glotzer
Summary: In this study, hard truncated triangular bipyramids self-assemble into seven different colloidal clathrate crystals, consisting of cages that are either empty or occupied by guest particles. Monte Carlo simulations reveal that the crystallization occurs through the compartmentalization of entropy between low- and high-entropy subsystems for the host and guest particles. The researchers also use entropic bonding theory to design host-guest colloidal clathrates with explicit interparticle attraction for experimental realization.
Article
Biochemistry & Molecular Biology
Franz Waibl, Klaus R. Liedl, Bernhard Rupp
Summary: Many macromolecular structure models in the PDB contain biologically relevant small molecule ligands with incorrect cis-trans stereochemistry. The errors may stem from deficiencies in stereochemical restraint files or negligence during model building. Awareness, identification, and correction of these errors are crucial to prevent inadvertent use of incorrect models.
Article
Chemistry, Inorganic & Nuclear
Reinhard Thaler, Holger Kopacka, Klaus Wurst, Thomas Mueller, Dennis F. Dinu, Klaus R. Liedl, Florian R. Neururer, Stephan Hohloch, Benno Bildstein
Summary: This article reports on the synthesis and properties of boron-substituted tromancenium salts, revealing their potential for novel synthetic applications.
Correction
Biochemistry & Molecular Biology
Monica L. Fernandez-Quintero, Patrick K. Quoika, Florian S. Wedl, Clarissa A. Seidler, Katharina B. Kroell, Johannes R. Loeffler, Nancy D. Pomarici, Valentin J. Hoerschinger, Alexander Bujotzek, Guy Georges, Hubert Kettenberger, Klaus R. Liedl
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sebastian Fuehrer, Jana Unterhauser, Ricarda Zeindl, Reiner Eidelpes, Monica L. Fernandez-Quintero, Klaus R. Liedl, Martin Tollinger
Summary: PR-10 proteins are a major cause of food allergic reactions. This study analyzes the structural flexibility of thirteen PR-10 proteins from prevalent plant food sources and reveals that they have inherently flexible protein backbones in solution, with protein-specific extent of flexibility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ferenc Torok, Kamer Tezcan, Ludovica Filippini, Monica L. Fernandez-Quintero, Lucia Zanetti, Klaus R. Liedl, Raphaela S. Drexel, Joerg Striessnig, Nadine J. Ortner
Summary: Germline gain-of-function missense variants in the CACNA1D gene can cause severe neurodevelopmental disorders with or without endocrine symptoms. We report a 4-week-old newborn with a novel de novo missense variant F747S in the Cav1.3 alpha 1-subunit, which is associated with a prominent jittering phenotype, developmental delay, elevated aldosterone level, and transient hypoglycemia. Functional experiments confirmed the pathogenicity of the variant and revealed significant changes in channel gating. The increased sensitivity to the L-type Ca2+ channel blocker isradipine suggests its potential as a treatment option for carriers of this mutation.
HUMAN MOLECULAR GENETICS
(2023)
Article
Chemistry, Physical
Dennis F. Dinu, Martin Tschoepe, Benjamin Schroeder, Klaus R. Liedl, Guntram Rauhut
Summary: Rotational constants and centrifugal distortion constants are essential parameters in molecular spectroscopy, providing valuable information about a molecule's rotational or rovibrational spectrum. This study presents an approach that combines ab initio calculations with fitting procedures to accurately determine these parameters, resulting in excellent agreement with experimental data.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Rafael Eduardo Oliveira Rocha, Diego Cesar Batista Mariano, Tiago Silva Almeida, Leon Sulfierry CorreaCosta, Pedro Henrique Camargo Fischer, Lucianna Helene Santos, Ernesto Raul Caffarena, Carlos Henrique da Silveira, Leonida M. Lamp, Monica Lisa Fernandez-Quintero, Klaus Roman Liedl, Raquel Cardoso De Melo-Minardi, Leonardo Henrique Franca de Lima
Summary: In this study, the molecular basis of the thermostabilization of the Paenibacillus polymyxa GH1 beta-glucosidase by two-point mutations was investigated through molecular dynamics simulations and computational analyses. Three classic mechanisms were found to contribute to the stabilization of the thermostable mutants.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Clarissa A. Seidler, Janik Kokot, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: In this study, the conformational diversity of four VHH variants and their binding to hen egg-white lysozyme (HEL) were investigated. It was found that with an increase in affinity, the stability of the VHH structure increased and the residues contributing to antigen binding underwent significant changes. In addition, it was observed that the investigated nanobodies followed the conformational selection paradigm, with the binding competent conformation pre-existing within the structural ensembles without the presence of the antigen.
Article
Biochemistry & Molecular Biology
Nancy D. Pomarici, Roberta Cacciato, Janik Kokot, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: This study investigates the evolution of immunoglobulin isotypes, highlighting the preserved features and the parts that have mutated over time. Coupled residues in the evolution process are crucial for maintaining the immunoglobulin fold and interactions with other domains. By comparing biophysical properties across different animal classes and isotypes, conserved residues in evolution can be identified. This study offers a general overview of the evolution of immunoglobulin isotypes and advances the understanding of their characteristic biophysical properties for guiding protein design.
Article
Biochemistry & Molecular Biology
Barbara A. Math, Franz Waibl, Leonida M. Lamp, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: Antibodies have emerged as a promising class of therapeutics, with diabodies being a popular novel antibody format. Molecular dynamics simulations reveal high conformational flexibility in the relative orientation of the two F-v domains in diabodies. Introduction of disulfide bonds rigidifies the structure and alters antigen binding properties, particularly in the CDR-H2 loop dynamics.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Food Science & Technology
Ricarda Zeindl, Annika L. Franzmann, Monica L. Fernandez-Quintero, Clarissa A. Seidler, Valentin J. Hoerschinger, Klaus R. Liedl, Martin Tollinger
Summary: Allergies related to kiwi consumption are on the rise, with cross-reactivity with birch pollen being a major factor. This study determined the three-dimensional structures of PR-10 proteins in kiwi fruits and found that they closely resemble the major allergen in birch pollen. Structural differences were observed compared to another kiwi allergen, Act d 11. Additionally, the study identified the presence of phenolic compound pyrogallol in kiwi proteins.
Article
Allergy
Florian Hofer, Anna-Lena Fischer, Anna S. Kamenik, Franz Waibl, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: The profilin allergen family is a class of proteins that are found in plants, viruses, and various eukaryotes. They have a conserved structural fold but exhibit differences in their biophysical properties. In this study, molecular dynamics simulations were performed to investigate the functional differences of three profilin allergens. It was found that these differences are related to conformational flexibility and thermal stability, emphasizing the importance of flexibility in understanding the biophysical differences between structurally similar allergens.
FRONTIERS IN ALLERGY
(2022)
Meeting Abstract
Biophysics
Martin C. Heiss, Monica L. Fernandez-Quintero, Yousra El Ghaleb, Simone Pelizzari, Petronel Tuluc, Marta Campiglio, Klaus R. Liedl, Bernhard E. Flucher
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Yousra El Ghaleb, Nadine J. Ortner, Wilfried Posch, Monica L. Fernandez-Quintero, Wietske E. Tuinte, Stefania Monteleone, Henning J. Draheim, Klaus R. Liedl, Doris Wilflingseder, Joerg Striessnig, Petronel Tuluc, Bernhard E. Flucher, Marta Campiglio
BIOPHYSICAL JOURNAL
(2022)