Abstract：
:Successful biologics must satisfy multiple properties including activity and particular physicochemical features that are globally defined as developability. These multiple properties must be simultaneously optimized in a very broad design space of protein sequences and buffer compositions. In this context, artificial intelligence (AI), and especially machine learning (ML), have great potential to accelerate and improve the optimization of protein properties, increasing their activity and safety as well as decreasing their development time and manufacturing costs. We highlight the emerging applications of ML in biologics discovery and development, focusing on protein engineering, early biophysical screening, and formulation. We discuss the power of ML in extracting information from complex datasets and in reducing the necessary experimental effort to simultaneously achieve multiple quality targets. We finally anticipate possible future interventions of AI in several steps of the biological landscape.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Narayanan H,Dingfelder F,Butté A,Lorenzen N,Sokolov M,Arosio Pdoi
10.1016/j.tips.2020.12.004subject
Has Abstractpub_date
2021-01-23 00:00:00eissn
0165-6147issn
1873-3735pii
S0165-6147(20)30285-6pub_type
杂志文章,评审abstract：:It has been suggested that G protein-coupled receptors can act as proton transporters, with the activated G protein-coupled receptor transporting H+ across the membrane from the extracellular side to the cytoplasm. In this article, Paul Nederkoorn, Henk Timmerman and Gabriëlle Donné-Op den Kelder summarize the various...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)89008-2
更新日期：1995-05-01 00:00:00
abstract：:Pairing orphan G-protein-coupled receptors (GPCRs) to potential ligands found in tissue extracts or in libraries of synthetic compounds has identified an ever-increasing number of transmitters, some of which are novel, some of which were previously known and, more recently, some of which are unexpected. These discover...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2004.11.005
更新日期：2005-01-01 00:00:00
abstract：:The breast cancer resistance protein [BCRP (also known as ABCG2)] belongs to the ATP binding cassette (ABC) family of transmembrane drug transporters. BCRP has a broad substrate specificity and actively extrudes a wide variety of drugs, carcinogens and dietary toxins from cells. Situated in the apical plasma membrane ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.11.007
更新日期：2006-01-01 00:00:00
abstract：:Efforts to model and reengineer the putative binding sites of G-protein-coupled receptors (GPCRs) have led to an approach that combines small-molecule 'classical' medicinal chemistry and gene therapy. In this approach, complementary structural changes (e.g. based on novel ionic or H-bonds) are made in the receptor and...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.01.006
更新日期：2007-03-01 00:00:00
abstract：:The current classification for 5-HT2 receptors accommodates three subtypes. In addition to the originally defined 5-HT2 receptor, sanctuary is now provided for the structurally related 5-HT1c receptor (now 5-HT2c) and at least one atypical 5-HT receptor subtype. The strong functional union of this family is reflected ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)88991-9
更新日期：1995-03-01 00:00:00
abstract：:In the past 20 years we have learned a great deal about GABAA receptor (GABAAR) subtypes, and which behaviors are regulated or which drug effects are mediated by each subtype. However, the question of where GABAARs involved in specific drug effects and behaviors are located in the brain remains largely unanswered. We ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.04.003
更新日期：2018-08-01 00:00:00
abstract：:Several clinical studies document a greater discrimination between asthmatic and healthy subjects in bronchial responsiveness to a range of stimuli such as cold air, distilled water and sodium metabisulphite, than to conventional bronchoconstrictor agonists including histamine and methacholine. One of the mechanisms t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01261-9
更新日期：1998-11-01 00:00:00
abstract：:Kinin B1 and B2 receptors are central to the aetiology of pain and inflammation. Constitutive B2 receptors are commonly associated with the acute phase of inflammation and nociception, whereas the inducible B1 receptors are mostly linked to the chronic or persistent phase (or both). Therefore, selective, orally active...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.10.007
更新日期：2006-12-01 00:00:00
abstract：:Dimerization is fairly common in the G-protein-coupled receptor (GPCR) superfamily. First attempts to rationalize this phenomenon gave rise to an idea that two receptors in a dimer could be necessary to bind a single molecule of G protein or arrestin. Although GPCRs, G proteins and arrestins were crystallized only in ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2008.02.004
更新日期：2008-05-01 00:00:00
abstract：:Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice wit...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.12.005
更新日期：2011-03-01 00:00:00
abstract：:Thiol-based drugs are considered as mucolytics because they decrease the viscosity and mostly decrease the elasticity of bronchial secretions by reducing disulfide bonds in proteins. However, they can also act as antioxidant drugs directly through free sulfhydryl groups that serve as a source of reducing equivalents, ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2019.04.015
更新日期：2019-07-01 00:00:00
abstract：:In the conventional view, GABA acts at either ionotropic GABAA or metabotropic GABAB receptors. Recently, novel ionotropic GABA receptors that are composed of rho-subunits have been identified in the vertebrate retina. These bicuculline- and baclofen-insensitive GABA receptors are frequently called GABAC, following an...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01413-3
更新日期：2000-01-01 00:00:00
abstract：:Within five years of discovering endothelin (ET-1) in 1988, the first report of an orally available ET receptor antagonist was published. Within twelve years, bosentan, the first ET receptor antagonist to gain marketing authorization, was made available for the treatment of pulmonary artery hypertension (PAH). Since t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.10.002
更新日期：2007-11-01 00:00:00
abstract：:Biogenic amines and amino acids have been implicated in central cardiovascular homeostasis. Initially, drugs were injected into the brain and their effects on blood pressure were investigated. Other approaches allowed endogenous neurotransmitters released in the extracellular space of brain structures involved in card...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：
更新日期：1996-10-01 00:00:00
abstract：:Since the cloning and expression of many of the G protein-coupled receptors during the 1980s, there has been a massive increase in our understanding of many aspects of their function. The use of molecular biology to engineer and express mutant receptors has made it possible to determine key amino acids involved in rec...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01231-0
更新日期：1998-08-01 00:00:00
abstract：:The hippocampus is a crucial player across several learning and memory domains, and is highly vulnerable to alterations during aging. Several products of neurotransmitter genes and neuromodulator genes (which play important parts in mediating and maintaining cognitive ability as a function of age) are expressed in hip...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.10.002
更新日期：2011-01-01 00:00:00
abstract：:The importance of the inhibitory neurotransmitter, GABA, within higher centres of the mammalian brain is unquestionable. However, its role within the spinal cord is of equal significance. There have been numerous studies over the past two decades that have established GABA as a neurotransmitter at both post- and presy...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(96)01013-9
更新日期：1996-12-01 00:00:00
abstract：:From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one o...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2010.08.006
更新日期：2010-12-01 00:00:00
abstract：:Central nervous system (CNS) drug development has been plagued by a failure to translate effective therapies from the lab to the clinic. There are many potential reasons for this, including poor understanding of brain pharmacokinetic (PK) and pharmacodynamic (PD) factors, preclinical study flaws, clinical trial design...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2020.09.002
更新日期：2020-11-01 00:00:00
abstract：:Although an established regulator of many cellular functions, the phosphoinositide phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2) appears to have evaded the attention of drug-discovery companies. An increasing number of reports have identified potential links between PtdIns(4,5)P2-mediated signalling pathways...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.10.004
更新日期：2005-12-01 00:00:00
abstract：:During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.02.008
更新日期：2016-05-01 00:00:00
abstract：:Muscarinic agonists open potassium-selective K(ACh) channels in cardiac myocytes of pacemaker or atrial origin. Receptor activation is coupled to channel opening by a membrane bound guanine nucleotide-binding protein (GK) through a process that does not require cytoplasmic intermediates. We have used the muscarinic po...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：
更新日期：1989-12-01 00:00:00
abstract：:Attempts to develop neuroprotective treatments for neurodegenerative disorders have not yet been clinically successful. Axonal degeneration has been recognized as a predominant driver of disability and disease progression in central nervous system (CNS) diseases such as amyotrophic lateral sclerosis (ALS), multiple sc...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2020.01.006
更新日期：2020-04-01 00:00:00
abstract：:Current concepts of the mechanisms underlying many of the pharmacological effects of ethanol on the CNS involve disruption of ion channel function via the interaction of ethanol with specific hydrophobic sites on channel subunit proteins. Of particular clinical importance is the development of tolerance and dependence...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01268-1
更新日期：1998-12-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is an incurable disease that arises from the progressive loss of motoneurons. Even when caused by a single gene defect, as in the case of mutations in the enzyme Cu-Zn superoxide dismutase (SOD1), ALS is the result of a complex cascade that involves crosstalk among motoneurons, glia...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.03.009
更新日期：2006-05-01 00:00:00
abstract：:New classes of drugs modifying Ca2+ channel activity have become available, this may enlarge the clinical utilities that have been associated with established Ca2+ channel antagonists such as the dihydropyridines (for example, nifedipine). Two such classes are reviewed by Michael Spedding, Barry Kenny and Pierre Chate...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)89002-1
更新日期：1995-04-01 00:00:00
abstract：:Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intramitochondrial calcium (Ca(2+)) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca(2+) home...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2010.08.007
更新日期：2010-12-01 00:00:00
abstract：:Bioluminescence resonance energy transfer has developed in recent years as a new technique to study protein-protein interactions. Protein partners of interest are tagged with either luciferase or green fluorescent protein (GFP). Non-radiative energy transfer between the excited luciferase and the GFP permits the study...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(02)02062-x
更新日期：2002-08-01 00:00:00
abstract：:K(+) channels are macromolecules embedded in biological membranes, where they play a key role in cellular excitability and signal transduction pathways. Knowledge of their structure should help improve our understanding of their function and lead to the design of therapeutic compounds. Most pharmacological and structu...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/S0165-6147(03)00080-4
更新日期：2003-05-01 00:00:00
abstract：:The tachykinin family has recently been extended by the discovery of a third tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1, endokinin A and endokinin B) that have a widespread peripheral distribution and a tachykinin NK(1) receptor selectivity. This and the identification of other tach...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2003.11.005
更新日期：2004-01-01 00:00:00
