Advancing Molecular Dynamics: Toward Standardization, Integration, and Data Accessibility in Structural Biology.

Molecular dynamics (MD) simulations have become a valuable tool in structural biology, offering insights into complex biological systems that are difficult to obtain through experimental techniques alone. The lack of available data sets and structures in most published computational work has limited other researchers' use of these models. In recent years, the emergence of online sharing platforms and MD database initiatives favor the deposition of ensembles and structures to accompany publications, favoring reuse of the data sets.

Myomerger Induces Membrane Hemifusion and Regulates Fusion Pore Expansion.

Membrane fusion is a crucial mechanism in a wide variety of important events in cell biology from viral infection to exocytosis. However, despite many efforts and much progress, cell-cell fusion has remained elusive to our understanding. Along the life of the fusion pore, large conformational changes take place from the initial lipid bilayer bending, passing through the hemifusion intermediates, and ending with the formation of the first nascent fusion pore.

When MELD Meets GaMD: Accelerating Biomolecular Landscape Exploration.

We introduce Gaussian accelerated MELD (GaMELD) as a new method for exploring the energy landscape of biomolecules. GaMELD combines the strengths of Gaussian accelerated molecular dynamics (GaMD) and modeling employing limited data (MELD) to navigate complex energy landscapes. MELD uses replica-exchange molecular simulations to integrate limited and uncertain data into simulations via Bayesian inference.

Intrinsic Disorder in α-Synuclein Regulates the Exocytotic Fusion Pore Transition.

Today, it is widely accepted that intrinsic disorder is strongly related to the cell cycle, during mitosis, differentiation, and apoptosis. Of particular interest are hybrid proteins possessing both structured and unstructured domains that are critical in human health and disease, such as α-synuclein. In this work, we describe how α-synuclein interacts with the nascent fusion pore as it evolves toward expansion.

Artificial stabilization of the fusion pore by intra-organelle styrene-maleic acid copolymers.

Styrene-maleic acid copolymers have become an advantageous detergent-free alternative for membrane protein isolation. Since their discovery, experimental membrane protein extraction and purification by keeping intact their lipid environment has become significantly easier. With the aim of identifying new applications of these interesting copolymers, their molecular binding and functioning mechanisms have recently become intense objects of study.

Cholesterol plays a decisive role in tetraspanin assemblies during bilayer deformations.

The tetraspanin family plays key roles in many physiological processes, such as, tumour invasion, cell motility, virus infection, cell attachment and entry. Tetraspanins function as molecular scaffolds organized in microdomains with interesting downstream cellular consequences. However, despite their relevance in human physiology, the precise mechanisms of their various functions remain elusive.

The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore.

Fusion pores serve as an effective mechanism to connect intracellular organelles and release vesicle contents during exocytosis. A complex lipid rearrangement takes place as membranes approximate, bend, fuse, and establish a traversing water channel to define the fusion pore, linking initially isolated chambers. Thermodynamically, the process is unfavorable and thought to be mediated by specialized proteins.

Order-disorder skewness in alpha-synuclein: a key mechanism to recognize membrane curvature.

Currently, membrane curvature is understood as an active mechanism to control cells spatial organization and activity. Protein processes involved in sensing and generating curvature are therefore of major interest. In this work, we have studied α-synuclein interactions with a model lipid bilayer, inducing curvature in a controlled manner and describing protein responses at molecular level.