Article
Biochemistry & Molecular Biology
Meng-Che Li, Ying-Jie Liu, Kuang-Cheng Hsu, Tse-Hsueh Lin, Chih-Wei Lin, Jia-Cherng Horng, Sheng-Kai Wang
Summary: This article investigates how the interaction between fluorine atoms alters protein structures and develops approaches to synthesize fluorinated peptides. The study systematically explores the effects of the number, location, and types of fluorine groups on the conformation of polyproline peptides.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Susanna Monti, Cheherazade Trouki, Giovanni Barcaro
Summary: We employed reactive molecular dynamics simulations and principal component analysis to obtain a clearer understanding of the interactions and motions of CO2 molecules and metal-organic framework components. Our simulations revealed the gate-opening/closing phenomenon, possible CO2 coordinations at the metal centers, diffusion steps inside the MOF channels, motions of the linkers, and the effects of their concerted rearrangements on CO2 relocations.
Article
Chemistry, Physical
Sung Jun Hong, Hoje Chun, Jehyun Lee, Byung-Hyun Kim, Min Ho Seo, Joonhee Kang, Byungchan Han
Summary: This study demonstrates the effective development of ML-FFs for the polymer PTFE, showing excellent consistency with density functional theory calculations for longer chain structures. When integrated with molecular dynamics simulations, the ML-FF successfully describes various physical properties of a PTFE bundle.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Yechan Noh, Narayana R. Aluru
Summary: Ion transport is crucial for cell proliferation, energy conversion, and homeostasis in living systems. This mechanism has inspired various nanofluidic applications, such as electricity harvesting, molecular sensors, and molecular separation. Through extensive molecular dynamics simulations, we investigated ion conduction across flexible 2D nanoporous membranes and found that the microscopic fluctuations of these membranes significantly increase ion conductance. Our analysis revealed that when the membrane fluctuated within a specific frequency range, the ion hydration was destabilized, leading to improved ion conduction. The dynamic coupling between the fluctuating membrane and ions plays a crucial role in ion conduction across 2D nanoporous membranes.
Article
Biochemistry & Molecular Biology
Martina Lenarcic Zivkovic, Martin Gajarsky, Katerina Bekova, Petr Stadlbauer, Lukas Vicherek, Magdalena Petrova, Radovan Fiala, Ivan Rosenberg, Jiri Sponer, Janez Plavec, Lukas Trantirek
Summary: Our recent study demonstrates the formation of an unprecedented pseudocircular G-hairpin (PGH) structure in Saccharomyces cerevisiae telomeric DNA. High-resolution NMR structure of a novel PGH family member reveals atomistic details on the junction between ssDNA and the PGH unit, providing insights into minimal sequence requirements for PGH formation. Time-resolved NMR data suggest a complex kinetic partitioning mechanism for PGH folding and the existence of K+ ion-dependent folding intermediates, explaining cation-type-dependent formation and hysteresis observed in previous studies.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Medicinal
Sandeep Lohan, Dindyal Mandal, Wonsuk Choi, Anastasia G. Konshina, Rakesh K. Tiwari, Roman G. Efremov, Innokentiy Maslennikov, Keykavous Parang
Summary: The study reports the synthesis of amphiphilic membrane-active peptides with broad-spectrum antibacterial activity, particularly effective against drug-resistant bacteria. The cyclic peptides were found to be more stable compared to their linear counterparts, and capable of disrupting bacterial cell membranes. Nuclear magnetic resonance spectroscopy and molecular dynamics simulation revealed the interaction mechanisms between these peptides and cell membranes.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Felsis Angelene Daison, Nitheeshkumar Kumar, Siranjeevi Balakrishnan, Kavyashree Venugopal, Sangamithra Elango, Pandian Sokkar
Summary: This study demonstrates that amphiphilic kaempferol derivatives with basic functional groups show excellent antibacterial activities by targeting negatively charged bacterial membranes. Molecular dynamics simulations and free energy change calculations reveal that these compounds can form pores in the bilayer to exert their antimicrobial effects.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Taichi Inagaki, Shinji Saito
Summary: In this paper, a new hybrid method called potential scaling HMC (PS-HMC) is introduced to study complex chemical processes. By modulating the trajectory and gradually flattening the potential energy surface, the PS-HMC method is capable of constructing the canonical ensemble with a multimodal distribution. Applications to different molecular processes demonstrate the feasibility and features of this new method.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
Zidan Zhang, Ram Krishna, Everett S. Zofchak, Nico Marioni, Harnoor S. Sachar, Venkat Ganesan
Summary: In this study, equilibrium and non-equilibrium atomistic simulations were used to investigate the influence of anion chemistry on conductivity, dynamical correlations, and ion transport mechanisms in polymeric ionic liquids. The results showed an inverse correlation between anion self-diffusivities, ionic mobilities, and anion size for spherical anions. While some larger asymmetric anions had higher diffusivities than smaller spherical anions, their diffusivities and mobilities did not exhibit a direct correlation with anion volumes. The conductivity and anion dynamical correlations also followed the same trends as the diffusivity and mobility of anions. All the systems examined displayed positively correlated motion among anions, indicating a contribution that enhances conductivity beyond the ideal Nernst-Einstein value. Analysis of ion transport mechanisms demonstrated very similar hopping characteristics among spherical anions despite differences in their sizes.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Medicinal
Sergio Boneta, Kernel Arafet, Vicent Moliner
Summary: This study investigated the enzymatic biodegradation of PET at an atomic level using molecular dynamics simulations. Two hydrolases, Ideonella sakaiensis 201-F6 and leaf-branch compost cutinase, showed degradation activity towards PET. The study revealed a characteristic four-step degradation pathway for both enzymes, with LCC-ICCG variant outperforming PETase possibly due to its ability to work at higher temperatures and its intrinsic relationship with the crystallinity grade of the polymer.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Rafael G. Viegas, Murilo N. Sanches, Alan A. A. Chen, Fernando V. Paulovich, Angel E. Garcia, Vitor B. P. Leite
Summary: Molecular dynamics (MD) simulations are powerful tools for studying the folding pathways of biomolecules. In this study, we used MD simulations to investigate the folding of an RNA tetraloop and analyzed the dynamics using the energy landscape visualization method (ELViM). Our results provide insights into the folding process of the tetraloop and demonstrate the potential of ELViM for studying biomolecules.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Felix Mayr, Milan Harth, Ioannis Kouroudis, Michael Rinderle, Alessio Gagliardi
Summary: This Perspective discusses the potential of novel machine learning techniques in exploring optoelectronic materials, and their application in accelerating calculations and providing experimental guidance. It also outlines the prospects of machine-learned molecular dynamics potentials, physically informed neural networks, and generative methods based on existing work.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biophysics
Liang Sun, Simin Wang, Fujia Tian, Haoqi Zhu, Liang Dai
Summary: The study reveals that melittin peptides can adopt T-and U-conformations in lipid bilayers, with T-pores having lower energy, larger pore diameter, and higher permeability compared to U-pores. However, T-pores occur less frequently in simulations due to their slower formation kinetics. Both types of pores are stable and permeable, with potential for enhancing antibacterial ability through optimization.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Arvind Ramanathan, Heng Ma, Akash Parvatikar, S. Chakra Chennubhotla
Summary: Recent developments in artificial intelligence and machine learning techniques have shown promise in integrating structural biology studies of intrinsically disordered protein ensembles. These proteins challenge traditional structure-function paradigms and require a combination of experimental techniques and simulations to gain insights into their functional mechanisms.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Chemistry, Physical
Elena Kolodzeiski, Saeed Amirjalayer
Summary: The study introduces an on-the-fly training algorithm for automating force field parametrization, addressing challenges in highly dynamic and interlocked structures. This method provides a fast, automated scheme for force field parametrization and accurately models equilibrium and out-of-equilibrium properties of flexible molecules.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Eric Fagerberg, Samuel Lenton, Tommy Nylander, Tilo Seydel, Marie Skepo
Summary: This study investigates the dynamical properties of Histatin 5, an intrinsically disordered protein, under self-crowding conditions. Quasi-elastic neutron scattering and molecular dynamics simulations are used to analyze the diffusion behavior. The results show that diffusion decreases significantly under crowding, possibly due to aggregation at higher protein concentrations. The temperature effects largely follow Stokes-Einstein behavior. Simple geometric considerations fail to predict diffusion rates accurately, while simulations show some agreement with experiments. The scaling law previously used for globular proteins is found inadequate for Histatin 5, highlighting the distinct characteristics of intrinsically disordered proteins.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Caroline Kampmeyer, Sven Larsen-Ledet, Morten Rose Wagnkilde, Mathias Michelsen, Henriette K. M. Iversen, Sofie V. Nielsen, Soren Lindemose, Alberto Caregnato, Tommer Ravid, Amelie Stein, Kaare Teilum, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: This study reveals that disease-linked missense variants destabilize protein structure and depend on molecular chaperones for degradation, providing insights into protein degradation mechanisms.
Article
Biophysics
Francesco Pesce, Estella A. Newcombe, Pernille Seiffert, Emil E. Tranchant, Johan G. Olsen, Christy R. Grace, Birthe B. Kragelund, Kresten Lindorff-Larsen
Summary: Diffusion measurements by pulsed-field gradient NMR and fluorescence correlation spectroscopy can be used to probe the hydrodynamic radius of proteins. To tackle the accuracy uncertainty issue in computing the hydrodynamic radius from atomic coordinates, conformational ensembles of intrinsically disordered proteins were built and compared with measurements of compaction. The Kirkwood-Riseman equation was found to provide the best description of the hydrodynamic radius probed by pulsed-field gradient NMR ex-periments.
BIOPHYSICAL JOURNAL
(2023)
Review
Oncology
Amanda B. Abildgaard, Sofie Nielsen, Inge Bernstein, Amelie Stein, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Accurate diagnosis and clinical interpretation of individual variants are crucial for the treatment of Lynch syndrome, a heritable cancer disease. Traditional protein variant classification methods are complex, but recent developments in high-throughput technologies and computational prediction tools offer new possibilities for assessing variants of unknown significance and gaining mechanistic insights into the disease.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Amanda B. Abildgaard, Vasileios Voutsinos, Soren D. Petersen, Fia B. Larsen, Caroline Kampmeyer, Kristoffer E. Johansson, Amelie Stein, Tommer Ravid, Claes Andreasson, Michael K. Jensen, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and chaperone-binding regions may function as PQC degrons. A canonical Hsp70-binding motif, the APPY peptide, functions as a dose-dependent PQC degron in yeast and human cells. The number of exposed Hsp70-binding sites in the yeast proteome correlates with reduced protein abundance and half-life.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kristoffer E. Johansson, Bayan Mashahreh, Rasmus Hartmann-Petersen, Tommer Ravid, Kresten Lindorff-Larsen
Summary: Effective proteome homeostasis is crucial for cell and organism survival. Cells have efficient quality control systems to monitor and remove misfolded proteins. The nature and sequence properties of quality-control degrons are still unknown.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Audrone Valanciute, Lasse Nygaard, Henrike Zschach, Michael Maglegaard Jepsen, Kresten Lindorff-Larsen, Amelie Stein
Summary: Calculating changes in protein stability (AAG) is important for predicting the consequences of amino acid substitutions in protein engineering and interpreting genomic variants for disease risk. This study investigates the accuracy of AAG values predicted on homology models compared to crystal structures, and finds that they are equally accurate as long as the sequence identity of the model template to the target protein is at least 40%. The results show that stability calculations performed on homology models can substitute for those on crystal structures with acceptable accuracy.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Fia B. Larsen, Matteo Cagiada, Jonas Dideriksen, Amelie Stein, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Catechol-O-methyltransferase (COMT) is an important enzyme involved in the metabolism of neurotransmitters and catecholamine drugs, and its variation can affect pharmacokinetics and drug availability.
Review
Biotechnology & Applied Microbiology
Yixin Rong, Sheila Ingemann Jensen, Kresten Lindorff-Larsen, Alex Toftgaard Nielsen
Summary: The expression of correctly folded and functional heterologous proteins is crucial in biotechnological production processes. Bacterial platform organisms like E. coli are commonly used due to their proven suitability at an industrial scale, but can suffer from protein aggregation and low functional protein levels. This review explores cellular mechanisms influencing protein folding and expression across different organisms, and discusses experimental methods to improve protein folding, such as codon optimization and chaperone co-production.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Biochemistry & Molecular Biology
Caroline Kampmeyer, Martin Gronbaek-Thygesen, Nicole Oelerich, Michael H. Tatham, Matteo Cagiada, Kresten Lindorff-Larsen, Wouter Boomsma, Kay Hofmann, Rasmus Hartmann-Petersen
Summary: Lysine is a common amino acid in the human proteome, but there are proteins that lack lysine residues. These lysine deserts are common in intrinsically disordered proteins involved in the ubiquitin-proteasome system. Introducing lysine residues can increase ubiquitylation of these proteins, and their stability and function may be affected. This avoidance of lysine residues may be an evolutionary mechanism to prevent unnecessary ubiquitylation in proteins closely involved with the ubiquitylation machinery.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Chemistry, Medicinal
Eric Fagerberg, Marie Skepo
Summary: Coarse-graining is commonly used to reduce computational cost in simulations, but it is known to have lower transferability and accuracy for systems beyond its parametrization scope. In this study, we compared the performance of a bead-necklace model and a modified Martini 2 model, both coarse-grained models, using a set of intrinsically disordered proteins with different degrees of coarse-graining. The results showed that the naive expectation of the least coarse-grained model performing the best was not true, indicating that a more advanced model is not necessarily better in model choice.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Kristoffer E. Johansson, Kresten Lindorff-Larsen, Jakob R. Winther
Summary: Identifying amino acid substitutions that improve both stability and function of a protein is a challenge in protein engineering. The Global Multi-Mutant Analysis (GMMA) method is used to identify beneficial substitutions across a large library of protein variants by analyzing multiply-substituted variants. Experimental results showed that the top-ranking substitutions progressively enhanced the function of GFP. Large libraries of multiply-substituted variants could provide valuable information for protein engineering.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Amanda E. Skog, Giacomo Corucci, Mark D. Tully, Giovanna Fragneto, Yuri Gerelli, Marie Skepo
Summary: Histatin 5 is a protein in saliva that acts as a defense against oral candidiasis. It forms a protein cushion under a model bilayer due to electrostatic interactions. Changing the number of histidines in the peptide sequence affects the penetration depth of the peptide into the bilayer.
Article
Biochemistry & Molecular Biology
Yulian Gavrilov, Andreas Prestel, Kresten Lindorff-Larsen, Kaare Teilum
Summary: Slow conformational changes are important for protein function, but their impact on the overall folding stability is not well understood. This study investigates the effects of L49I and I57V substitutions on the slow conformational dynamics of CI2. The results show that these substitutions have minimal impact on the structure of the excited state, but the stability of the excited state is influenced by the stability of the main state. The interactions between substituted residues and water molecules play a role in linking subtle structural changes to slow conformational changes in the protein.
Article
Biology
F. Emil Thomasen, Matthew J. Cuneo, Tanja Mittag, Kresten Lindorff-Larsen
Summary: Speckle-type POZ protein (SPOP) is a key protein in the ubiquitin proteasome system, with important roles in cell-cycle control, development, and cancer pathogenesis. This study combines small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations to characterize the conformational ensembles and oligomeric states of SPOP. The results suggest that SPOP oligomers behave as rigid, helical structures with flexible substrate-binding domains.
