Recep Adiyaman
Weekly Digest February 20, 2026 · 19 min read

Weekly Digest: Feb 16 - Feb 20, 2026

A curated summary of the top protein engineering and structure prediction signals from Feb 16 - Feb 20, 2026.

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Daily curated signals from arXiv, PubMed, and BioRxiv.

🧬 Weekly Recap

Feb 16 - Feb 20, 2026

Missed a day? Here are the top research signals and tools from Monday to Friday, summarized in one place.


🏆 Top Signals of the Week

🗓️ Monday, Feb 16

DeepFold-PLM: accelerating protein structure prediction via efficient homology search using protein language models.

🧬 Abstract

Motivation Protein structure prediction has been revolutionized and generalized with the advent of cutting-edge AI methods such as AlphaFold, but reliance on computationally intensive multiple sequence alignments (MSA) remains a major limitation. Results We introduce DeepFold-PLM, a novel framework that integrates advanced protein language models with vector embedding databases to enhance ultra-fast MSA construction, remote homology detection, and protein structure prediction. DeepFold-PLM utilizes high-dimensional embeddings and contrastive learning, significantly accelerate MSA generation, achieving 47 times faster than standard methods, while maintaining prediction accuracy comparable to AlphaFold. In addition, it enhances structure prediction by extending modeling capabilities to multimeric protein complexes, provides a scalable PyTorch-based implementation for efficient large-scale prediction. Our method also effectively increases sequence diversity (Neff = 8.65 versus 4.83 with JackHMMER) enriching coevolutionary information critical for accurate structure prediction. DeepFold-PLM thus represents a versatile and practical resource that enables high-throughput applications in computational structural biology. Availability and implementation Source codes and user-friendly Python API of all modules of DeepFold-PLM publicly available at https://github.com/DeepFoldProtein/DeepFold-PLM.

Why it matters: Critical for improving fold accuracy and reducing structural uncertainty in de novo design.

🗓️ Tuesday, Feb 17

AlphaFold2-Guided Cyclic Peptide Stabilizer Design to Target Protein-Protein Interactions.

🧬 Abstract

The control and modulation of protein-protein interactions (PPIs) is of central importance for the majority of biological processes and most biomedical applications. Stabilization of PPIs, besides inhibition, is of growing pharmaceutical interest. Due to their small size, drug-like organic molecules may not provide sufficient interaction surfaces to allow for high-affinity dual binding to both partners of a protein-protein complex. Cyclic peptides offer larger interaction surfaces, making them a promising class of stabilizers of PPIs. We have developed a computational protocol to rapidly and systematically design cyclic peptides that optimize not only the interaction with one target protein but simultaneously optimize the dual binding to two protein partners. The cyclic peptide generation is based on a modified AlphaFold2-based peptide design approach and combines confidence scoring with force field-based scoring using Molecular Dynamics simulations. The performance of the method is tested on protein-protein complexes with known cyclic peptide binders and stabilizers. In addition, the approach is used to design cyclic peptides that can act as bifunctional molecules, recruiting the cellular protein degradation system to a target protein. The designed cyclic peptides achieve similar or better calculated interaction scores than known binders and exhibit well-balanced interactions with both protein partners. The design protocol is generally applicable to cyclic peptide design for modulating or inducing protein-protein association and could be useful for many biomedical design efforts.

🗓️ Wednesday, Feb 18

Molecular docking: a computational approach for the discovery of novel targets against visceral leishmaniasis.

🧬 Abstract

The protozoan parasite Leishmania donovani is a major causative agent of visceral leishmaniasis (VL), a lethal disease posing significant public health challenges globally. Existing anti-VL drugs have become increasingly ineffective due to rising drug resistance, underscoring the urgent need for novel and effective therapeutic candidates. Computational approaches offer rapid and systematic methods for identifying potential drug targets and supporting rational drug design. This review discusses in silico molecular docking studies targeting various Leishmania proteins and their inhibitors, alongside the in vitro and in vivo validation of selected compounds, emphasizing their crucial roles in advancing antileishmanial drug discovery. In the review, we have focused on a molecular docking study and explored potential compounds with high binding energy toward protein targets of Leishmania. Following the in silico screening, our review highlights compounds that exhibit both in vitro and in vivo antileishmanial properties, allowing for an assessment of their therapeutic efficacy. Different Software is available for molecular docking, has been mentioned in the review. Overall conclusion of this review supports the computational approach in drug discovery before the in vitro and in vivo study, which can save cost and time efficiency as well.

🗓️ Thursday, Feb 19

Structure-Guided Engineering of High-Affinity Antibodies Against Zika Virus Using Deep Learning and Molecular Dynamics.

🧬 Abstract

Zika virus (ZIKV) remains a global health threat, for which no licensed antiviral treatment has been available. In this study, we employed in silico approaches to optimize monoclonal antibodies targeting the Zika virus envelope protein (ZIKV E) in the Domain III (DIII) region, which is crucial for receptor binding and virus entry. A high-resolution crystal structure of ZIKV E in complex with the neutralizing antibody ZV-64 was used as a template for designing a library of antibody variants through targeted double-point mutations. The variants were systematically evaluated for stability, binding affinity, solubility, and protein-protein interaction potential using FoldX, DeepPurpose, SoluProt, and molecular docking. Among all the mutants, Variants-213 and -206 were identified as the top candidates, exhibiting the most favorable predicted binding affinity and solubility compared to the control antibody. The molecular dynamics simulations further revealed the structural stability of the two mutant variants, in which Variant-206 showed a predicted binding energy (-76.90 kcal/mol) along with higher conformational flexibilities. The findings demonstrate the use of computational antibody engineering to identify potentially high-affinity therapeutics against ZIKV, providing a foundation for future experimental validation and therapeutic development against ZIKV.

🗓️ Friday, Feb 20

A New Insight into the Study of Neural Cell Adhesion Molecule (NCAM) Polysialylation Inhibition Incorporated the Molecular Docking Models into the NMR Spectroscopy of a Crucial Peptide-Ligand Interaction.

🧬 Abstract

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. During the NCAM polysialylation process, polysialyltransferases (polySTs), such as polysialyltransferase IV (ST8SIA4) or polysialyltransferase II (ST8SIA2), can catalyze the addition of CMP-sialic acid (CMP-Sia) to the NCAM to form polysialic acid (polySia). In this study, the docking models of polysialyltransferase IV (ST8Sia4) protein and different ligands were predicted using Alphafold 3 and DiffDock servers, and the prediction accuracy was further verified using the NMR experimental spectra of the interactions between polysialyltransferase domain (PSTD), a crucial peptide domain in ST8Sia4, and a different ligand. This combination strategy provides new insights into a quick and effective screening for inhibitors of tumor cell migration.

Why it matters: Enhances small-molecule or peptide docking accuracy for targeted drug discovery.


📚 All Papers & Quick Reads

🗓️ Monday, Feb 16

🗓️ Tuesday, Feb 17

🗓️ Wednesday, Feb 18

🗓️ Thursday, Feb 19

🗓️ Friday, Feb 20


🛠️ Tools & Datasets

  • 🛠 Tool: Foldseek - Ultra-fast structural search and clustering engine.
  • 🛠 Tool: MMseqs2 - Fast and sensitive sequence search and clustering suite.
  • 💾 Dataset: AlphaFold Structure Database - 200M+ predicted structures from DeepMind/EMBL-EBI.
  • 💾 Dataset: Uniprot Knowledgebase - The world’s most comprehensive resource for protein sequence and annotation.
  • 🛠 Tool: HHSuite - Remote homology detection with HMM-HMM comparison.
  • 💾 Dataset: PDB-REDO - Optimized protein structure database with refined models.
  • 🛠 Tool: MAFFT - Multiple sequence alignment with high speed and accuracy.
  • 💾 Dataset: CATH - Hierarchical protein domain classification for structure and function.
  • 🛠 Tool: Clustal Omega - Scalable multiple sequence alignment for protein families.
  • 💾 Dataset: SCOPe - Curated structural classification of proteins for fold analysis.
  • 🛠 Tool: Rosetta - Protein modeling, docking, and design suite.
  • 💾 Dataset: Pfam - Protein families database with curated multiple sequence alignments.

🤖 AI in Research Recap


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