Solubility-aware protein binding peptide design using AlphaFold

Kosugi, Takatsugu; Ohue, Masahito

doi:10.1101/2022.05.14.491955

Cited by 4 publications

(1 citation statement)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Optimizing aqueous solubility is essentially a pragmatic procedure that can be achieved by replacing unnecessary hydrophobic amino acids with charged and polar residues to adjust the isoelectric point without sacrificing its biological activities. [94,95]…”

Section: Strategies To Overcome the Disadvantagesmentioning

confidence: 99%

Review on therapeutic potential of peptides: Advancements in synthesis methods, linear and cyclic peptides, and strategies for overcoming challenges

Lalani,

Tivari,

Jain

et al. 2024

Peptide Science

View full text Add to dashboard Cite

In the realm of therapeutic peptides, tremendous progress has been achieved in the last two decades. The building block of peptides that is, ‘Amino Acid’ has been modified by various chemical modifications such as side‐chain alteration in linear peptides, cyclization, back‐bone modification, pro‐drug moiety, conjugation with heterocycles, and natural products to make peptides a foremost candidate as a therapeutic drug. Since the advent of insulin in 1922, peptides have immensely affected the development of the pharmaceutical industry giving rise to the peptide‐based drug industry. In recent years, peptides having antimicrobial, antiviral, anti‐tumor, anti‐inflammatory, anti‐aging, and antioxidant properties have developed. Also, it has now entered as a potent candidate in the field of oncology and also become a valuable tool as a radiolabeled peptide for the detection of various diseases. Generally, peptides were extracted from natural sources in the olden days, but presently work is directed towards finding alternate and sustainable ways for developing synthetic peptides. The present review covers the discussion about the historic evaluation of peptides, available effective synthetic processes, current advancements, use of bioinformatic tools, computational strategies, and the methodology to overcome the barrier for making peptides the potent candidate for the future world.

show abstract

Section: Strategies To Overcome the Disadvantagesmentioning

confidence: 99%

Review on therapeutic potential of peptides: Advancements in synthesis methods, linear and cyclic peptides, and strategies for overcoming challenges

Lalani,

Tivari,

Jain

et al. 2024

Peptide Science

View full text Add to dashboard Cite

show abstract

Designing Collagen-Binding Peptide with Enhanced Properties Using Hydropathic Free Energy Predictions

et al. 2023

View full text Add to dashboard Cite

Collagen is fundamental to a vast diversity of health functions and potential therapeutics. Short peptides targeting collagen are attractive for designing modular systems for site-specific delivery of bioactive agents. Characterization of peptide–protein binding involves a larger number of potential interactions that require screening methods to target physiological conditions. We build a hydropathy-based free energy estimation tool which allows quick evaluation of peptides binding to collagen. Previous studies showed that pH plays a significant role in collagen structure and stability. Our design tool enables probing peptides for their collagen-binding property across multiple pH conditions. We explored binding features of currently known collagen-binding peptides, collagen type I alpha chain 2 sense peptide (TKKTLRT) and decorin LRR-10 (LRELHLNNN). Based on these analyzes, we engineered a collagen-binding peptide with enhanced properties across a large pH range in contrast to LRR-10 pH dependence. To validate our predictions, we used a quantum-dots-based binding assay to compare the coverage of the peptides on type I collagen. The predicted peptide resulted in improved collagen binding. Hydropathy of the peptide–protein pair is a promising approach to finding compatible pairings with minimal use of computational resources, and our method allows for quick evaluation of peptides for binding to other proteins. Overall, the free-energy-based tool provides an alternative computational screening approach that impacts protein interaction search methods.

show abstract

Reinventing Therapeutic Proteins: Mining a Treasure of New Therapies

Niazi

Mariam

2023

Biologics

View full text Add to dashboard Cite

Reinventing approved therapeutic proteins for a new dose, a new formulation, a new route of administration, an improved safety profile, a new indication, or a new conjugate with a drug or a radioactive source is a creative approach to benefit from the billions spent on developing new therapeutic proteins. These new opportunities were created only recently with the arrival of AI/ML tools and high throughput screening technologies. Furthermore, the complex nature of proteins offers mining opportunities that are not possible with chemical drugs; bringing in newer therapies without spending billions makes this path highly lucrative financially while serving the dire needs of humanity. This paper analyzes several practical reinventing approaches and suggests regulatory strategies to reduce development costs significantly. This should enable the entry of hundreds of new therapies at affordable costs.

show abstract

Solubility-aware protein binding peptide design using AlphaFold

Cited by 4 publications

References 50 publications

Review on therapeutic potential of peptides: Advancements in synthesis methods, linear and cyclic peptides, and strategies for overcoming challenges

Review on therapeutic potential of peptides: Advancements in synthesis methods, linear and cyclic peptides, and strategies for overcoming challenges

Designing Collagen-Binding Peptide with Enhanced Properties Using Hydropathic Free Energy Predictions

Reinventing Therapeutic Proteins: Mining a Treasure of New Therapies

Contact Info

Product

Resources

About