OrganL: Dynamic Triangulation of Biomembranes using Curved Elements
We describe a method for simulating biomembranes of arbitrary shape. In contrast to other dynamically triangulated surface (DTS) algorithms, our method provides a rich, quasi tangent-continuous, yet local description of the surface. We use curved Nagata triangles, which we generalize to cubic order to achieve the requisite flexibility. The resulting interpolation can be constructed locally without iterations, at the cost of having only approximate tangent continuity away from the vertices. This allows us to provide a parallelized and fine-tuned Monte Carlo implementation. As a first example of the potential benefits of the...
Source: Biophysical Journal - May 5, 2024 Category: Physics Authors: Christoph Allolio Bal ázs Fábián Mark Dostal ík Source Type: research
A role for conformational changes in enzyme catalysis
Biophys J. 2024 May 3:S0006-3495(24)00310-2. doi: 10.1016/j.bpj.2024.04.030. Online ahead of print.ABSTRACTThe role played by conformational changes in enzyme catalysis is controversial. In addition to examining specific enzymes, studying formal models can help identify the conditions under which conformational changes promote catalysis. Here, we present a model demonstrating how conformational changes can break a generic trade-off due to the conflicting requirements of successive steps in catalytic cycles, namely high specificity for the transition state to accelerate the chemical transformation and low affinity for the p...
Source: Biophysical Journal - May 5, 2024 Category: Physics Authors: Olivier Rivoire Source Type: research
Fluorescence lifetime imaging microscopy of flexible and rigid dyes probes the biophysical properties of synthetic and biological membranes
Biophys J. 2024 May 2:S0006-3495(24)00313-8. doi: 10.1016/j.bpj.2024.04.033. Online ahead of print.ABSTRACTSensing of the biophysical properties of membranes using molecular reporters has recently regained wide-spread attention. This was elicited by the development of new probes of exquisite optical properties and increased performance, combined with developments in fluorescence detection. Here, we report on fluorescence lifetime imaging (FLIM) of various rigid and flexible fluorescent dyes to probe the biophysical properties of synthetic and biological membranes at steady state as well as upon the action of external membr...
Source: Biophysical Journal - May 4, 2024 Category: Physics Authors: Rafael B Lira Laura S Dillingh Jan-Jacob Schuringa Gokhan Yahioglu Klaus Suhling Wouter H Roos Source Type: research
Parkinson's Disease-associated mutations in α-synuclein alters its lipid-bound state
In this report, we use a tryptophan fluorescence assay to measure the binding of the α-helices of these PD-associated mutants to lipid membranes within the lipid depletion regime. We characterize the binding behavior of each helix, revealing that generally, the PD-associated mutants shift the equilibrium bound state away from the N-terminal helix of the protein toward Helix 2 at lower lipid concentrations. Altogether, our results indicate that disruption to the equilibrium binding of the two α-helices of α-synuclein could play a role in PD progression.PMID:38702883 | DOI:10.1016/j.bpj.2024.05.002 (Source: Biophysical Journal)
Source: Biophysical Journal - May 4, 2024 Category: Physics Authors: Sofiya Maltseva Daniel Kerr Miah Turke Erin J Adams Ka Yee C Lee Source Type: research
Simulations predict preferred Mg < sup > 2+ < /sup > coordination in a nonenzymatic primer extension reaction center
Biophys J. 2024 May 2:S0006-3495(24)00312-6. doi: 10.1016/j.bpj.2024.04.032. Online ahead of print.ABSTRACTThe mechanism by which genetic information was copied prior to the evolution of ribozymes is of great interest because of its importance to the origin of life. The most effective known process for the nonenzymatic copying of an RNA template is primer extension by a two-step pathway in which 2-aminoimidazole activated nucleotides first react with each other to form an imidazolium-bridged intermediate that subsequently reacts with the primer. Reaction kinetics, structure-activity relationships, and X-ray crystallography...
Source: Biophysical Journal - May 4, 2024 Category: Physics Authors: Shriyaa Mittal Collin Nisler Jack W Szostak Source Type: research
Fluorescence lifetime imaging microscopy of flexible and rigid dyes probes the biophysical properties of synthetic and biological membranes
Biophys J. 2024 May 2:S0006-3495(24)00313-8. doi: 10.1016/j.bpj.2024.04.033. Online ahead of print.ABSTRACTSensing of the biophysical properties of membranes using molecular reporters has recently regained wide-spread attention. This was elicited by the development of new probes of exquisite optical properties and increased performance, combined with developments in fluorescence detection. Here, we report on fluorescence lifetime imaging (FLIM) of various rigid and flexible fluorescent dyes to probe the biophysical properties of synthetic and biological membranes at steady state as well as upon the action of external membr...
Source: Biophysical Journal - May 4, 2024 Category: Physics Authors: Rafael B Lira Laura S Dillingh Jan-Jacob Schuringa Gokhan Yahioglu Klaus Suhling Wouter H Roos Source Type: research
Parkinson's Disease-associated mutations in α-synuclein alters its lipid-bound state
In this report, we use a tryptophan fluorescence assay to measure the binding of the α-helices of these PD-associated mutants to lipid membranes within the lipid depletion regime. We characterize the binding behavior of each helix, revealing that generally, the PD-associated mutants shift the equilibrium bound state away from the N-terminal helix of the protein toward Helix 2 at lower lipid concentrations. Altogether, our results indicate that disruption to the equilibrium binding of the two α-helices of α-synuclein could play a role in PD progression.PMID:38702883 | DOI:10.1016/j.bpj.2024.05.002 (Source: Biophysical Journal)
Source: Biophysical Journal - May 4, 2024 Category: Physics Authors: Sofiya Maltseva Daniel Kerr Miah Turke Erin J Adams Ka Yee C Lee Source Type: research
Simulations predict preferred Mg < sup > 2+ < /sup > coordination in a nonenzymatic primer extension reaction center
Biophys J. 2024 May 2:S0006-3495(24)00312-6. doi: 10.1016/j.bpj.2024.04.032. Online ahead of print.ABSTRACTThe mechanism by which genetic information was copied prior to the evolution of ribozymes is of great interest because of its importance to the origin of life. The most effective known process for the nonenzymatic copying of an RNA template is primer extension by a two-step pathway in which 2-aminoimidazole activated nucleotides first react with each other to form an imidazolium-bridged intermediate that subsequently reacts with the primer. Reaction kinetics, structure-activity relationships, and X-ray crystallography...
Source: Biophysical Journal - May 4, 2024 Category: Physics Authors: Shriyaa Mittal Collin Nisler Jack W Szostak Source Type: research
Protein Condensates in the Secretory Pathway: Deciphering Biophysical Interactions and Functional Significance
Biophys J. 2024 May 2:S0006-3495(24)00311-4. doi: 10.1016/j.bpj.2024.04.031. Online ahead of print.ABSTRACTThe emergence of phase separation phenomena among macromolecules has identified biomolecular condensates as fundamental cellular organizers. These condensates concentrate specific components and accelerate biochemical reactions without relying on membrane boundaries. While extensive studies have revealed a large variety of nuclear and cytosolic membraneless organelles, we are witnessing a surge in the exploration of protein condensates associated with the membranes of the secretory pathway, such as the endoplasmic ret...
Source: Biophysical Journal - May 3, 2024 Category: Physics Authors: Felix Campelo Javier Vera Lillo Julia von Blume Source Type: research
Protein Condensates in the Secretory Pathway: Deciphering Biophysical Interactions and Functional Significance
Biophys J. 2024 May 2:S0006-3495(24)00311-4. doi: 10.1016/j.bpj.2024.04.031. Online ahead of print.ABSTRACTThe emergence of phase separation phenomena among macromolecules has identified biomolecular condensates as fundamental cellular organizers. These condensates concentrate specific components and accelerate biochemical reactions without relying on membrane boundaries. While extensive studies have revealed a large variety of nuclear and cytosolic membraneless organelles, we are witnessing a surge in the exploration of protein condensates associated with the membranes of the secretory pathway, such as the endoplasmic ret...
Source: Biophysical Journal - May 3, 2024 Category: Physics Authors: Felix Campelo Javier Vera Lillo Julia von Blume Source Type: research
Cryo-EM images of phase separated lipid bilayer vesicles analyzed with a machine learning approach
Biophys J. 2024 Apr 30:S0006-3495(24)00291-1. doi: 10.1016/j.bpj.2024.04.029. Online ahead of print.ABSTRACTLateral lipid heterogeneity (i.e., raft formation) in biomembranes plays a functional role in living cells. Three-component mixtures of low- and high-melting lipids plus cholesterol offer a simplified experimental model for raft domains in which a liquid-disordered (Ld) phase coexists with a liquid-ordered (Lo) phase. Using such models, we recently showed that cryogenic electron microscopy (cryo-EM) can detect phase separation in lipid vesicles based on differences in bilayer thickness. However, the considerable nois...
Source: Biophysical Journal - May 1, 2024 Category: Physics Authors: Karan D Sharma Milka Doktorova M Neal Waxham Frederick A Heberle Source Type: research
Cryo-EM images of phase separated lipid bilayer vesicles analyzed with a machine learning approach
Biophys J. 2024 Apr 30:S0006-3495(24)00291-1. doi: 10.1016/j.bpj.2024.04.029. Online ahead of print.ABSTRACTLateral lipid heterogeneity (i.e., raft formation) in biomembranes plays a functional role in living cells. Three-component mixtures of low- and high-melting lipids plus cholesterol offer a simplified experimental model for raft domains in which a liquid-disordered (Ld) phase coexists with a liquid-ordered (Lo) phase. Using such models, we recently showed that cryogenic electron microscopy (cryo-EM) can detect phase separation in lipid vesicles based on differences in bilayer thickness. However, the considerable nois...
Source: Biophysical Journal - May 1, 2024 Category: Physics Authors: Karan D Sharma Milka Doktorova M Neal Waxham Frederick A Heberle Source Type: research
A bupropion modulatory site in Gloeobacter violaceus ligand-gated ion channel
Biophys J. 2024 Apr 27:S0006-3495(24)00289-3. doi: 10.1016/j.bpj.2024.04.027. Online ahead of print.ABSTRACTBupropion is an atypical antidepressant and smoking cessation drug that causes adverse effects such as insomnia, irritability, and anxiety. Bupropion inhibits dopamine and norepinephrine reuptake transporters and eukaryotic cation-conducting pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine (nACh) and serotonin type 3A (5-HT3A) receptors, at clinically relevant concentrations. Here, we demonstrate that bupropion also inhibits a prokaryotic homolog of pLGICs, the Gloeobacter violaceus liga...
Source: Biophysical Journal - April 28, 2024 Category: Physics Authors: Hoa Quynh Do Elham Pirayesh Garren Ferreira Akash Pandhare Zackary Ryan Gallardo Michaela Jansen Source Type: research
Mapping the contribution of C-linker domain to gating polarity in CNBD channels
Biophys J. 2024 Apr 26:S0006-3495(24)00284-4. doi: 10.1016/j.bpj.2024.04.022. Online ahead of print.ABSTRACTIon channels of the cyclic nucleotide-binding domain (CNBD) family play a crucial role in the regulation of key biological processes, such as photoreception and pacemaking activity in the heart. These channels exhibit high sequence and structural similarity but differ greatly in their functional responses to membrane potential. The CNBD family includes hyperpolarization-activated ion channels (HCN) and depolarization-activated ether-à-go-go (EAG) channels. Structural and functional studies show that the differences ...
Source: Biophysical Journal - April 28, 2024 Category: Physics Authors: Jenna L Lin Yongchang Chang Debanjan Tewari John Cowgill Baron Chanda Source Type: research
Molecular simulations and NMR reveal how lipid fluctuations affect membrane mechanics
Biophys J. 2024 Apr 27:S0006-3495(24)00280-7. doi: 10.1016/j.bpj.2024.04.018. Online ahead of print.NO ABSTRACTPMID:38679022 | DOI:10.1016/j.bpj.2024.04.018 (Source: Biophysical Journal)
Source: Biophysical Journal - April 28, 2024 Category: Physics Authors: Milka Doktorova George Khelashvili Rana Ashkar Michael F Brown Source Type: research
