Assessing AF2's ability to predict structural ensembles of proteins.

Recent breakthroughs in protein structure prediction have enhanced the precision and speed at which protein configurations can be determined. Additionally, molecular dynamics (MD) simulations serve as a crucial tool for capturing the conformational space of proteins, providing valuable insights into their structural fluctuations. However, the scope of MD simulations is often limited by the accessible timescales and the computational resources available, posing challenges to comprehensively exploring protein behaviors.

The Role of Force Fields and Water Models in Protein Folding and Unfolding Dynamics.

Protein folding is a fascinating, not fully understood phenomenon in biology. Molecular dynamics (MD) simulations are an invaluable tool to study conformational changes in atomistic detail, including folding and unfolding processes of proteins. However, the accuracy of the conformational ensembles derived from MD simulations inevitably relies on the quality of the underlying force field in combination with the respective water model.

Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines.

Antibodies and other new antibody-like formats have emerged as one of the most rapidly growing classes of biotherapeutic proteins. Understanding the structural features that drive antibody function and, consequently, their molecular recognition is critical for engineering antibodies. Here, we present the structural architecture of conventional IgG antibodies alongside other formats.

CDR loop interactions can determine heavy and light chain pairing preferences in bispecific antibodies.

As the current biotherapeutic market is dominated by antibodies, the design of different antibody formats, like bispecific antibodies, is critical to the advancement of the field. In contrast to monovalent antibodies, which consist of two identical antigen-binding sites, bispecific antibodies can target two different epitopes by containing two different antigen-binding sites. Thus, the rise of new formats as successful therapeutics has reignited the interest in advancing and facilitating the efficient production of bispecific antibodies.

Mutation of Framework Residue H71 Results in Different Antibody Paratope States in Solution.

Characterizing and understanding the antibody binding interface have become a pre-requisite for rational antibody design and engineering. The antigen-binding site is formed by six hypervariable loops, known as the complementarity determining regions (CDRs) and by the relative interdomain orientation (V-V). Antibody CDR loops with a certain sequence have been thought to be limited to a single static canonical conformation determining their binding properties.