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--- regsys [2012/10/28 10:54] – [Stage B. General structure check & preparation] sanmark
+++ regsys [2013/10/19 11:36] (current) – [Process outline] rkiss
@@ Line 1: / Line 1: @@
-====== The mcule structure registration system ======
+====== Mcule Advanced Curation (MAC) ======
-The mcule structure registration system is primarily designed to handle chemical structures coming from different data sources, mainly from chemical suppliers, and load the structures into the mcule database. This is a non-trivial task which requires a careful structure check and preparation procedure. To reach a high curation level, the registration system should ensure database quality in terms of structure correctness, uniqueness and reliability as well as maintain a high level of data standardization.
+The mcule database is curated by **MAC (Mcule Advanced Curation)** that involves a rigorous molecule registration system based on more than 80 structural checks, standardization, preparation and correction steps. MAC guarantees high quality search results and avoids common errors arising from mis-drawn and incorrect structures that can critically affect the quality of computational calculations and the efficiency of experimental results.
-**Key features:** high level data curation, stereochemical standardization, robust novelty check and isomer detection, handling salts & organometallics
+**Key features of MAC:** high level data curation, stereochemical standardization, robust novelty check and isomer detection, correct handling of salts & organometallics
-===Registration challenges===
+Continue reading for more information about MAC, or check our presentations from the 244th National Meeting of American Chemical Society:
+[[http://mcule-blog.s3.amazonaws.com/acs12/mcule_ACS12_Phi_libraries.pdf|Evaluation of data quality in currently available compound libraries (slides)]]
+[[http://mcule-blog.s3.amazonaws.com/acs12/mcule_ACS12_libraries.jpg|Evaluation of data quality in currently available compound libraries (poster)]]
+==== Quality is important ====
+The design of screening libraries and the development of predictive drug discovery models **all start with a high quality database**. Chemical correctness is crucial because mis-drawn and imperfectly defined structures result in incorrect models, misleading predictions and inconsistent hits. Problematic structures should therefore be eliminated at the earliest possible stage from a drug discovery pipeline.
+The mcule structure registration system is primarily designed to correctly handle chemical structures coming from different data sources, mainly from chemical suppliers, and load the structures into the mcule database. This is a non-trivial task which requires a careful structure check and preparation procedure. To reach a high curation level, the registration system should ensure database quality in terms of structure correctness, uniqueness and reliability as well as maintain a high level of data standardization.
+**All molecules with an MCULE ID have been processed by MAC**. User uploaded molecules are not processed by MAC by default. We plan to enable this option in future.
+==== Registration challenges ====
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 ===== Process outline =====
-The whole registration process can be divided into seven different stages. It begins with the revision of stereo configurations, structure check/preparation steps (stage A, B) followed by component separation (stage C). Thereafter component uniqueness is checked and mcule IDs are assigned (stage D, E). This is performed with or without considering tautomerism and protonation, resulting the assignment of tautomer and protonation state independent [[mculeid|compound identifiers]] (stage D) as well as tautomer and protonation state dependent [[mculeid|structure identifiers]] (stage E). Finally, based on component identity, multicomponent entries are also registered at both the tautomer and protonation state independent (stage F) and dependent levels (stage G).
+The whole registration process can be divided into seven different stages. It begins with the revision of stereo configurations, structure check/preparation steps (stage A, B) followed by component separation (stage C). Thereafter component uniqueness is checked and mcule IDs are assigned (stage D, E). This is performed with or without considering tautomerism and protonation, resulting the assignment of tautomer and protonation state independent [[structurelevels|compound identifiers]] (stage D) as well as tautomer and protonation state dependent [[structurelevels|structure identifiers]] (stage E). Finally, based on component identity, multicomponent entries are also registered at both the tautomer and protonation state independent (stage F) and dependent levels (stage G).
 |Stage A |Enforcing [[stereonotations|standard stereo representation]]; non-standard stereo notations are changed, unreliable part of stereo configurations is removed (after consulting with chemical supplier) |
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 As a result, input entries as well as their components are registered at two levels: tautomer and protonation state independent [[structurelevels|compound level]] with tautomer detection and tautomer and protonation state dependent [[structurelevels|structure level]] without tautomer detection.
 ===== Registration process =====
@@ Line 137: / Line 151: @@
 In this stage we separate components of the incoming structure. In common salts counterions can be disconnected and separated from the main component automatically. Bonds to the main component are deleted and proper charges are placed on both components.
+{{ :regsys:reg_sys_9.png |}}
 ==== Stage D & E. Component registration ====
 //Summary: individual components’ structures are normalized, unique components are registered with new mcule IDs assigned at the tautomer and protonation state independent (D) and dependent (E) levels (steps in the D & E stages are very similar except for novelty check)//
@@ Line 145: / Line 160: @@
 In the mcule system there are [[stereonotations|four stereo configuration types]]: absolute, relative, racemic and unknown (the “unknown” type is used to denote uncertain configurations, where compound provider could not confirm that the configuration type is really absolute). They are assigned in the stereo clean-up stage, and these initially assigned types are inherited by the separated components. In these steps these assigned stereo configuration types as well as the stereo configurations are further processed: for those components having no stereocenters, stereo configuration types are removed, while the stereo configuration of components with stereocenters are normalized together with their stereo configuration types.
+{{ :regsys:reg_sys_10.png |}}
 Normalization is needed because certain configurations can be represented with multiple structures and/or [[stereonotations|stereo configuration types]]: replacing configurations around atoms and/or the configuration type can result in stereochemically equivalent structures. This can primarily happen when the configuration is only partially specified, containing atoms with both unknown/undefined and well-defined configurations. As a preparation step for the novelty check the same representative structures are selected from the set of structures with equivalent configurations.
@@ Line 156: / Line 173: @@
 In stage D we use a novelty check algorithm that is based on the InChI strings but can detect an even broader set of potential tautomers than a simple InChI comparison. The system is capable to fully prevent the registration of duplicates as long as they are prototopic tautomers.
+{{ :regsys:reg_sys_11.png |}}
 ==== Stage E & F. Multicomponent structure registration ====
 //Summary: additional checks are performed, component types are assigned, and unique structures are registered with new mcule IDs assigned at the tautomer and protonation state independent (F) and dependent (G) levels (steps in the F & G stages are very similar)//
@@ Line 172: / Line 190: @@
 In most cases the system is also capable of identifying the main components, which can serve as the input set for virtual screens.
+You can see below the index page of compound [[https://mcule.com/MCULE-3198812899/|MCULE-3198812899]]. This is a maleic and/or fumaric acid salt
+(uncertainty is marked by crossed double bond). Counter ions are marked, and component multiplicities are assigned correctly by the system.
+{{:regsys:reg_sys_12.png|}}